The Handiest Girlie Of All

Paralyzed woman gets robotic arm she controls with her mind

In a clinical trial, Cathy Hutchinson, who has been paralyzed for more than 14 years, used the BrainGate system to mentally control a robotic arm and reach for a drink. 

 

The stroke that disconnected Cathy Hutchinson’s brain from her body has kept her silent and unable to move for more than 14 years. But science is starting to change all that.

Researchers have connected the 58-year-old woman’s brain to a computer that runs a robotic arm. As Hutchinson sits at a table staring at a bottled drink and imagining the robot grabbing the bottle and bringing it to her mouth, the robot arm begins to move.

The robot is running on signals detected by sensors implanted in the part of Hutchinson’s brain that would normally control the movements of her right arm. The sensors pick up the sparking of nerve cells and send the signals to the computer which then translates them into commands for the robotic arm. Suddenly Hutchinson is able to do something she could only dream of before: As she thinks about getting herself a drink, the arm reaches over to the bottle and brings it to her lips, where she is able to sip the drink from a straw.

It’s the first time Hutchinson’s been able to do anything for herself since the stroke.

Hutchinson’s experiences, along with those of another quadriplegic patient, were described in a groundbreaking paper published Wednesday in Nature. Both patients are part of an ongoing government funded trial that is testing the new brain translation technology, BrainGate, which one day may free “locked-in” patients like Hutchinson and give functional limbs to amputees.

It will be years before BrainGate could be available to the general public. But Hutchinson’s happy to enjoy the future today. After realizing she could control the robot arm, she said she was “ecstatic.” Though Hutchinson cannot speak, she can type her thoughts through a device that takes its cues from her eye movements.

She’s optimistic about what the research might one day bring. “I would love to have robotic leg support,” she says.

 

What’s amazing is how researchers have “taught” their computer to essentially read Hutchinson’s thoughts.

The baby-aspirin sized sensor implanted in Hutchinson’s brain contains 96 hair-thin electrodes that record the sparking of neurons in the movement control center, the motor cortex.

The first step in the learning process is for the computer to “see” which neurons spark, and in what pattern, when a person picks up a bottle and brings it to her lips, explains the study’s lead researcher, Dr. Leigh R. Hochberg, a professor of engineering at Brown University, a researcher at the Providence VA Medical Center, a critical care neurologist at the Massachusetts General Hospital/Brigham and Women’s Hospital in Boston, and a visiting associate  professor of neurology at the Harvard Medical School.

Fortuitously, it doesn’t matter whether the person actually moves their limb or whether they’re merely imagining themselves doing it. So, for several trials, Hochberg and his colleagues had the computer observe the sparking patterns of neurons in Hutchinson’s brain as she watched the robot arm pick up the bottle and bring it to her lips.

Once the scientists had taught the computer which patterns would normally make Hutchinson’s arm reach out for the bottle of coffee, they hardwired them as the command for the robot arm to do the same thing – but with the signal coming directly from Hutchinson’s brain as she imagined herself grasping the cup and bringing it to her lips.

“Beyond this, our real dream for this research is for people with paralysis — from a brain stroke or spinal cord injury — to be able to one day reconnect the brain to the limbs,” Hochberg says.

Those kinds of injuries often leave a healthy brain disconnected from a healthy set of nerves that would normally control the movement of the limbs. So, the hope is that someday doctors might be able to reconnect things, like an electrician replacing a bit of shorted out wire.

For her part, Hutchinson is hoping that the researchers come up with a permanent, wireless implant and a way to reconnect her brain to her body.

She imagines what it would be like to cook and garden again. “I know that someday this will happen again,” she says.

 

MSNBC

Medical Board Adopts Controversial Stem Cell Rules

The Texas Medical Board today approved controversial new rules on the use of adult stem cells that have raised concerns over the possibility that Texans could receive therapies that have not yet been proven to work and that could be unsafe.

Researchers say the evidence of success of stem cell injections is anecdotal, and they advocate waiting for clinical trial results before allowing physicians to charge patients — typically tens of thousands of dollars — for the procedures.

The new guidelines allow for stem cell procedures as long as they are done for research and receive approval from an institutional review board, which can be private and for-profit. The rules also require that patients sign informed consent forms.

“I think there are some real problems with these rules,” said Leigh Turner, a professor at the University of Minnesota’s Center for Bioethics who commented on the rules before the board. “The protective mechanism that they’re focusing on isn’t going to do very much.” 

The rules’ supporters acknowledged the need for changes, such as better defining “stem cells,” but they said the rules would better protect Texas patients. Procedures are being performed now without oversight.

 

“Doing something at this point is better than doing nothing,” said Mario Salinas, director of Texans for Stem Cell Research, adding that “This is just the first step.”

Gov. Rick Perry has been a strong supporter of the adult stem cell industry, and he received a stem cell injection last July to treat his back pain. That same month, Perry sent a letter to the Medical Board chairman noting the “revolutionary potential that adult stem cell research and therapies have on our nation’s health, quality of life and economy.”  The rules approved today do not address the use of embryonic stem cells — a far more controversial procedure that has drawn moral and religious objections. 

Though bone marrow transplants, which use blood-forming stem cells, have been used effectively as treatment for decades, experts say other procedures remain experimental. The Medical Board’s proposed rules, published last month in the Texas Register, attracted criticism from the international journal Nature, which wrote in an editorial that the board should “make clear the need for clinical validation of adult stem cells.”

Because the rules had already been published in the Texas Register and stakeholders had provided input, the Medical Board could not make major changes today and faced a simple choice today: accept the rules or reject them.  

Even some board members who voted for the rules agreed that they weren’t perfect. But they said the rules improved on the current situation by adding a layer of protection for Texas patients.

“Right now, we’ve got essentially an emergency state, where there are a lot of concerns about the way stem cells are being used,” said Stanley Wang, a board member. “Our rule adds in at least the layer of [institutional review board] approval before a doctor can act.”

William Smythe, a board member who voted against the rules, agreed that guidelines are needed, but objected to the use of the procedures without additional research.

He added: “If Texas wants to be a leader in this area, there are other ways to do this. You want to add a layer of protection? Put a moratorium on the use of these agents until they’re proven.”

 

Texas Tribune

Texas Medical Board

Related articles

• Stem Cells Treatment Law In Texas Will Allow Doctors To Offer Experimental Treatments Without FDA Approval (inquisitr.com)
• Texas board mulls stem cell therapy restrictions - San Jose Mercury News (drugstoresource.wordpress.com)
• Texas OKs experimental stem cell therapy rules (medicalxpress.com)
• Texas - Perry - Stem Cells - New Ruling (repairstemcell.wordpress.com)

Study shows Alzheimers spreads like a virus in the brain

 

Alzheimer’s disease seems to spread like an infection from brain cell to brain cell, two new studies in mice have found. But instead of viruses or bacteria, what is being spread is a distorted protein known as tau.

The surprising finding answers a longstanding question and has immediate implications for developing treatments, researchers said. And they suspect that other degenerative brain diseases like Parkinson’s may spread in a similar way.

Alzheimer’s researchers have long known that dying, tau-filled cells first emerge in a small area of the brain where memories are made and stored. The disease then slowly moves outward to larger areas that involve remembering and reasoning.

But for more than a quarter-century, researchers have been unable to decide between two explanations. One is that the spread may mean that the disease is transmitted from neuron to neuron, perhaps along the paths that nerve cells use to communicate with one another. Or it could simply mean that some brain areas are more resilient than others and resist the disease longer.

The new studies provide an answer. And they indicate it may be possible to bring Alzheimer’s disease to an abrupt halt early on by preventing cell-to-cell transmission, perhaps with an antibody that blocks tau.

The studies, done independently by researchers at Columbia and Harvard, involved genetically engineered mice that could make abnormal human tau proteins, predominantly in the entorhinal (pronounced en-toh-RYE-nal) cortex, a sliver of tissue behind the ears, toward the middle of the brain, where cells first start dying in Alzheimer’s disease. As expected, tau showed up there. And, as also expected, entorhinal cortex cells in the mice started dying, filled with tangled, spaghettilike strands of tau.

Over the next two years, the cell death and destruction spread outward to other cells along the same network. Since those other cells could not make human tau, the only way they could get the protein was by transmission from nerve cell to nerve cell.

And that, said Dr. Samuel E. Gandy, associate director of the Alzheimer’s Disease Research Center at Mount Sinai School of Medicine in New York, was “very unexpected, very intriguing.”

Although the studies were in mice, researchers say they expect that the same phenomenon occurs in humans because the mice had a human tau gene and the progressive wave of cell death matched what they see in people with Alzheimer’s disease.

One study, by Karen Duff and Dr. Scott A. Small and their colleagues at the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Medical Center, was published on Wednesday in the journal PLoS One. The other, by Dr. Bradley T. Hyman, director of the Alzheimer’s Disease Research Center at Massachusetts General Hospital, and his colleagues, is to be published in the journal Neuron.

Both groups of researchers were inspired by the many observations over the years that Alzheimer’s starts in the entorhinal cortex and spreads.

But, said Dr. Small, “what do we mean by ‘spreads?’ ”

Researchers knew that something set off Alzheimer’s disease. The most likely candidate is a protein known as beta amyloid, which accumulates in the brain of Alzheimer’s patients, forming hard, barnaclelike plaques. But beta amyloid is very different from tau. It is secreted and clumps outside cells. Although researchers have looked, they have never seen evidence that amyloid spreads from cell to cell in a network.

Still, amyloid creates what amounts to a bad neighborhood in memory regions of the brain. Then tau comes in — some researchers call it “the executioner” — piling up inside cells and killing them. If some cells take longer than others to succumb to the bad neighborhood, that would explain the spread of the disease in the brain, and there would be no need to blame something odd, like the spread of tau from cell to cell.

Studies in humans, though, could not determine whether that hypothesis was correct. They involved autopsy and brain imaging studies and were “indirect and inconclusive,” Dr. Small said.

Looking at the brains of people who have died of the disease, Dr. Duff said, is like looking at a wrecked car and trying to figure out the accident’s cause. Faulty brakes? Broken struts?

The question of which hypothesis was correct — tau spreading cell to cell, or a bad neighborhood in the brain and cells with different vulnerabilities to it — remained unanswerable. Dr. Hyman said he tried for 25 years to find a good way to address it. One of his ideas was to find a patient or two who had had a stroke or other injury that severed the entorhinal cortex from the rest of the brain. If the patient developed Alzheimer’s in the entorhinal cortex — and it remained contained there — he would have evidence that the disease spread like an infection. But he never found such patients.

The solution came when researchers were able to develop genetically engineered mice that expressed abnormal human tau, but only in their entorhinal cortexes. Those mice offered the cleanest way to get an answer, said John Hardy, an Alzheimer’s researcher at University College London who was not involved in either of the new studies.

There is another advantage, too, Dr. Hyman said. The mice give him a tool to test ways to block tau’s spread — and that, he added, “is one of the things we’re excited about.”

But if tau spreads from neuron to neuron, Dr. Hardy said, it may be necessary to block both beta amyloid production, which seems to get the disease going, and the spread of tau, which continues it, to bring Alzheimer’s to a halt.

He and others are also asking if other degenerative diseases spread through the brain because proteins pass from nerve cell to nerve cell.

Dr. Hardy thought he saw provocative human evidence that it might be happening in Parkinson’s disease. Two Parkinson’s patients being treated by a colleague had fetal brain cells implanted to replace dead and dying neurons. When the patients died, years later, autopsies showed they still had the fetal cells, but they had balls of a Parkinson’s disease protein, synuclein, inside. The most obvious way that could happen, the researchers reasoned, was if the toxic protein had spread from the patient’s diseased cells to the healthy fetal cells. But they could not rule out the bad-neighborhood hypothesis.

Now, Dr. Hardy said, with the mouse studies, the issue of a bad neighborhood is settled. The answer in Alzheimer’s disease, he said, “is that isn’t possible.”

“That is what is different between these papers and all the others,” Dr. Hardy said. “It isn’t a bad neighborhood. It is contagion from one neuron to another.”

 

NY TIMES

Related articles

• Alzheimer's spreads like a virus in the brain, studies find (mercurynews.com)
• Alzheimer's discovery could curb spread of disease, researchers say (thestar.com)
• Role of rogue protein seen as clue to Alzheimer's cure (smh.com.au)

Government Funding of alternative treatments questioned

Some see tax dollar waste in spending by the National Center for Complementary and Alternative Medicine. The NCCAM director, though, sees a need for scientific attention.

Thanks to a $374,000 taxpayer-funded grant, scientists now know that inhaling lemon and lavender scents doesn't do a lot for our ability to heal a wound. For $666,000 in federal research money, we can be certain that distant prayer cannot heal AIDS. Americans also paid $406,000 to learn that squirting brewed coffee into someone's intestines doesn't help treat pancreatic cancer and $1.25 million to discover that massage makes people with advanced cancer feel better.

These and other dubious investigations were funded by the government's National Center for Complementary and Alternative Medicine. NCCAM, a small, little-known branch of the National Institutes of Health, was launched a dozen years ago to study alternative treatments that are used by the public but are not accepted by mainstream medicine.

Since its birth, the center has spent $1.4 billion, most of it on research. Millions of those dollars have been used to fund studies with questionable grounding in science, according to a review of hundreds of NCCAM grants and other documents reviewed by the Chicago Tribune.

"Some of these treatments were just distinctly made up out of people's imaginations," says Dr. Wallace Sampson, clinical professor emeritus of medicine at Stanford University."How can we justify wasting money on something like this when there are so many other things that are much more plausible and much more likely to result in real benefit?" adds Dr. David Gorski, a breast cancer researcher at Wayne State University in Detroit and vocal critic of NCCAM.

The director of the center and other advocates say it is worthwhile to use taxpayer dollars to study certain alternative treatments. "They deserve scientific attention," says NCCAM Director Josephine Briggs, a respected NIH researcher and physician who has headed NCCAM for nearly four years.

Briggs says that she's dedicated to evidence-based medicine and that the center, under her leadership, is committed to rigorous scientific studies. Besides, she says, the center's $128-million annual allotment amounts to less than half a percent of the total NIH budget.

The center's recently adopted strategic plan focuses on studies of supplements and other natural products, along with the effect of therapies like yoga, massage and acupuncture on pain and other symptoms. Studies of energy healing or distant prayer likely would not get funded by NCCAM today, Briggs says: "We are not your grandmother's NCCAM."

Yet many treatments that are being studied, like qigong and acupuncture, also involve the purported manipulation of a universal energy or life force that is incompatible with scientists' understanding of how the body works.

NCCAM's continuing interest in acupuncture comes even though many of its studies have found that acupuncture and similar therapies are no better than sham treatments at easing symptoms like pain and fatigue. To most scientists, that's a sign the treatments don't work — after all, drug companies can't sell medicines that work no better than a sugar pill.

Critics of the center say it's telling that NCCAM was conceived not by scientists clamoring to study alternative medicine but by Sen. Tom Harkin (D-Iowa), a member of the Senate subcommittee that helps oversee the NIH budget. In a 1998 speech, Harkin described watching acupuncture and acupressure ease the pain and violent hiccups of a brother dying of thyroid cancer.

"These are things I have seen with my own eyes," said Harkin, who also lost three other siblings to cancer. "When I see things like this, I ask, 'Why? Why aren't these things being researched?'"

NCCAM was created a few months later. The center's main mission was clear: Study alternative therapies and how they could be integrated into conventional treatment.

$43 billion a year

About 4 out of 10 American adults use some sort of alternative treatment, according to a 2007 survey by the U.S. Centers for Disease Control and Prevention. Mostly they reported taking supplements, practicing deep breathing exercises, going to a chiropractor or osteopath for spinal manipulation, meditating or getting massages. The out-of-pocket bill for these therapies adds up to about $43 billion a year, the survey found.

Conducting scientific studies to determine whether these treatments work is a valuable service, says Dr. Steven DeKosky, who sits on the NCCAM advisory council and is dean of the University of Virginia medical school. "I don't know who else would do that other than NCCAM."

DeKosky, a neurologist, received $25 million from NCCAM to help fund a study on whether ginkgo biloba can protect against dementia and Alzheimer's disease. He concluded that the popular supplement did not reduce the overall incidence of either condition in elderly people who were normal or already had mild cognitive impairment.

Such studies are conducted by randomly assigning some people to take the supplement being tested and giving others a placebo; volunteers don't know which group they're in, so that knowledge can't bias the results. Researchers compare the outcomes for both groups to see whether those who took the supplement were better off than those who took the dummy pill. This approach is widely accepted in the medical research community.

But when looking into "mind and body" medicine, NCCAM often argues that a treatment is valuable if patients report that it helped them — even if others receiving a sham treatment said the same.

For example, the center has spent millions on studies of acupuncture, in which tiny needles are inserted shallowly into the body to unblock the "vital energy" called qi, according to NCCAM's website. Many of those studies have found that true acupuncture performs no better than sham acupuncture, in which a person is fooled into thinking he is getting the real thing through the use of retractable needles or even toothpicks twirled on the skin.

People often report feeling less pain or being less fatigued regardless of whether they receive real or fake acupuncture, suggesting a placebo effect is at work. Yet NCCAM is pouring more research money into acupuncture.

"The intellectual dishonesty is just astounding," says Dr. Steven Novella, a neurologist at Yale School of Medicine and an NCCAM critic.

Briggs says it's difficult to design trials of complex therapies like acupuncture. "It is generally impossible to isolate a single element. A sham control in a mind-and-body study could easily miss answering the most important question of whether the patient experiences benefit."

Physicians who treat patients in pain say they welcome any new tools, especially ones without the side effects of narcotics. If that means offering a treatment that may be a placebo, so be it.

"We have lots of people out there with a problem that isn't being addressed with conventional approaches," says Daniel Cherkin, who researchers alternative medicine in Seattle and sits on the NCCAM advisory council. "What do we do with those people? To say we shouldn't do these things because it is a placebo denies them something safe and available and works."

Critics respond that it's not right to charge people hundreds or thousands of dollars for treatments that amount to nothing more than an elaborate placebo.

"It is essentially deluding somebody," says Sampson of Stanford. "In other parts of our social life, it is a crime."

LA TIMES

New Definition of Autism May Exclude Many, Study Suggests

 

 

 

Proposed changes in the definition of autism would sharply reduce the skyrocketing rate at which the disorder is diagnosed and may make it harder for many people who would no longer meet the criteria to get health, educational and social services, a new analysis suggests.

The definition is under review by an expert panel appointed by the American Psychiatric Association, which is completing work on the fifth edition of its Diagnostic and Statistical Manual of Mental Disorders. The D.S.M, as the manual is known, is the standard reference for mental disorders, driving research, treatment and insurance decisions.

The study results, presented on Thursday at a meeting of the Icelandic Medical Association, are still preliminary, but they offer the latest and most dramatic estimate of how tightening the criteria for autism could affect the rate of diagnosis. Rates of autism and related disorders like Asperger syndrome have taken off since the early 1980s, to prevalence rates as high as one in 100 children in some places. Many researchers suspect that these numbers are inflated because of vagueness in the current criteria.

“The proposed changes would put an end to the autism epidemic,” said Dr. Fred R. Volkmar, director of the Child Study Center at Yale University School of Medicine and an author of the new analysis. “We would nip it in the bud — think of it that way.”Experts working on the new definition — a group that formerly included Dr. Volkmar — strongly questioned the new estimate. “I don’t know how they’re getting those numbers,” said Catherine Lord, a member of the task force working on the diagnosis.

Previous projections have concluded that far fewer people would be excluded under the proposed diagnosis change, said Dr. Lord, director of the Institute for Brain Development, a joint project of NewYork-Presbyterian Hospital, Weill Cornell Medical College, Columbia University Medical Center and the New York Center for Autism.

Disagreement about the effect of the new definition will almost certainly increase scrutiny of the finer points of the psychiatric association’s changes to the manual The revisions are about 90 percent complete and will be final by December, according to Dr. David J. Kupfer, a professor of psychiatry at the University of Pittsburgh and chairman of the task force making the revisions.

At least a million children and adults have a diagnosis of autism or a related disorder, like Asperger syndrome or “pervasive developmental disorder, not otherwise specified” — or P.D.D.-N.O.S. People with Asperger’s or P.D.D.-N.O.S. endure some of the same social struggles as those with autism but do not meet the definition for the full-blown version. The proposed change would consolidate all three diagnoses under one category, autism spectrum disorder, eliminating Asperger syndrome and P.D.D.-N.O.S. from the manual. Under the current criteria a person can qualify for the diagnosis by exhibiting six or more of 12 behaviors; under the proposed definition, the person would have to exhibit three deficits in social interaction and communication and at least two repetitive behaviors — a much narrower menu.

Dr. Kupfer said the proposed changes were an attempt to clarify these permutations and put them under one name.

Hundreds of thousands of people receive state-backed special services to help offset the disorders’ disabling effects, which include learning and social problems, and the diagnosis is in many ways central to their lives. Close networks of parents have bonded over common experiences with children; and the children, too, may grow to find a sense of their own identity in their struggle with the disorder.

Mary Meyer, of Ramsey, N.J., said that a diagnosis of Asperger syndrome was crucial in getting her daughter, who is 37, access to services that have helped tremendously. “I’m very concerned about the change in diagnosis because I wonder if my daughter would even qualify now,” she said. “She’s on disability, which is partly based on the Asperger’s, and I’m hoping to get her into supportive housing, which also depends on her diagnosis.”

Mark Roithmayr, president of Autism Speaks, an advocacy organization, said that the proposed diagnosis should bring needed clarity but that the effect on services was not yet clear. “We need to carefully monitor the impact of these diagnostic changes on access to services and ensure that no one is being denied the services they need,” Mr. Roithmayr said by e-mail. “Some treatments and services are driven solely by a person’s diagnosis, while other services may depend on other criteria such as age, I.Q. level or medical history.”

In the new analysis, Dr. Volkmar, along with Brian Reichow and James McPartland, both at Yale, used data from a large 1993 study that served as the basis for the current criteria. They focused on 372 children and adults who were among the highest-functioning and found that over all, only 45 percent of them would qualify for the proposed autism spectrum diagnosis now under review. The focus on a high-functioning group may have slightly exaggerated that percentage, the authors acknowledge.

The likelihood of being left out under the new definition depended on the original diagnosis: About a quarter of those identified with classic autism in 1993 would not be so identified under the proposed criteria; about three quarters of those with Asperger’s would not qualify; and 85 percent of those with P.D.D.-N.O.S. would not.

Dr. Volkmar presented the preliminary findings on Thursday. The researchers will publish a broader analysis, based on a larger and more representative sample of 1,000 cases, later this year. Dr. Volkmar said that although the proposed diagnosis would be for disorders on a spectrum and implies a broader net, it focuses tightly on “classically autistic” children on the more severe end of the scale. “The major impact here is on the more cognitively able,” he said.

Dr. Lord said that the study numbers are probably exaggerated because the research team relied on old data, collected by doctors who were not aware of what kinds of behaviors the proposed definition requires. “It’s not that the behaviors didn’t exist, but that they weren’t even asking about them — they wouldn’t show up at all in the data,” Dr. Lord said.

New York Times

 

Related articles

• Autism, As I See It. (icantbrain.com)
• What is an autism spectrum disorder? (zocdoc.com)
• Adults with #Autism and other things. (mizreelmikkoi.wordpress.com)
• Understanding The Diagnostics Of Autism And Aspergers Syndrome (aspergersinfo.wordpress.com)

National MS Society Convenes Summit to Explore Vitamin D Trials to Prevent MS

Researchers and clinicians from around the globe gathered recently in Chicago to develop strategies for testing whether vitamin D supplements can prevent the development of MS. Participants discussed the latest findings relevant to vitamin D and MS and potential clinical trial designs, taking the first steps to making these exciting studies a reality. “Vitamin D and MS Prevention: An International Workshop,” was chaired by Colleen E. Hayes, PhD (University of Wisconsin-Madison) and Anne-Louise Ponsonby, PhD (Murdoch Children’s Research Institute, Canberra Australia), and was funded by the National MS Society.

 

Background:

Research is increasingly pointing to a reduced level of vitamin D in the blood as a risk factor for developing MS. Years ago, MS researchers wondered why MS occurs less often in regions of the world where exposure to sunlight is high. Dr. Hayes – a professor of biochemistry and microbiology – and colleagues suggested that vitamin D, which is made by cells in the skin in response to sunlight, may suppress the immune response involved in MS. She and others have since shown that in lab mice, vitamin D can reduce the effects of EAE, an MS-like disease. 

Epidemiologic studies (studies of who gets MS) have backed up laboratory studies. Dr. Ponsonby – an epidemiologist and public health physician – was a co-author of the Ausimmune Study, a comprehensive Australian study that showed that higher levels of sun exposure and higher blood levels of vitamin D were both associated with decreased risk of having a first demyelinating event, often the first indicator of subsequent MS. 

The National MS Society has led the way in pursuing this avenue of MS research, funding much of Dr. Hayes’ work, first funding the Ausimmune study, and now, a new clinical trial testing whether vitamin D can reduce disease activity in people who have MS. Read more on clinicaltrials.gov. 

The Meeting: Participants included experts in vitamin D studies, immunology, statistics, epidemiology, clinical MS research, pediatric MS, and MS biomarkers. The group began by bringing its vast experience to bear in discussing the promise and potential pitfalls of conducting “primary prevention studies” using vitamin D to potentially prevent MS before it occurs. 

“We are people from all over the world and we have one common purpose – to stop this disease,” noted Dr. Hayes. “The research that has been done by the people in this room and others provides us with strong evidence that vitamin D may help.”

Alberto Ascherio, MD, DrPH (Harvard School of Public Health) and colleagues have published pivotal studies relating to several MS risk factors. His 2006 study  – supported by the Society – compared levels of vitamin D in blood serum stored from military personnel during their service, and found that those with higher levels of vitamin D were at lower risk for later developing multiple sclerosis. Dr. Ascherio noted a major concern about designing vitamin D studies, based on his research. “Compliance is likely to be a major obstacle,” he said. “You have to worry about people in the placebo group that might take vitamin D anyway, and make the study powerful enough to account for that.” 

George Ebers, MD, FRCP(C) (University of Oxford) reported on findings “hot off the press” – his team recently confirmed an association between MS and a gene linked to vitamin D. Dr. Ebers cautioned that before beginning a study, “You absolutely need to know what the rate of MS is in your country,” noting that the reported rates of MS is increasing in some areas. 
Dr. Hayes reviewed basic research that could have a strong impact on planned studies. For example, female mice treated with vitamin D are protected from MS-like disease, but not male mice. “Normal estrogen may be essential for vitamin D benefits,” she said. Also, her research points to the immune messenger protein interleukin-10 as being essential for vitamin D protection from MS-like disease in mice. “Anything that destroys that pathway may undermine a treatment trial,” said Dr. Hayes. 

Jorge Correale, MD (Raul Carrea Institute for Neurological Research Argentina) discussed his research on the immune response and vitamin D. “Vitamin D is particularly reduced during relapses in people with MS,” he said, noting that administering vitamin D to cells isolated from people with MS resulted in modulation of immune “T cells” which have been previously implicated in MS activity. He noted that cells that reduce inflammation are activated by vitamin D and those that promote inflammation are suppressed.

Reinhold Vieth, PhD, FCACB (University of Toronto) has been studying vitamin D for decades. His team’s findings show that this vitamin is associated with decreased PSA (a marker for prostate cancer), and a decreased risk of breast cancer. His experience provided numerous important considerations for conducting vitamin D prevention trials in MS. “Vitamin D binding protein [a protein that helps to transport the vitamin within the body] acts as a safety buffer to prevent toxicity,” he said. “It protects the body from having too much vitamin D.” Dr. Vieth works with the team that found vitamin D supplements to be safe in small, early study of people with MS (Neurology 2010;75(5):480). 

Co-chair Dr. Ponsonby encouraged participants with her review of similar efforts undertaken to combat other diseases such as folate supplementation to mothers in pregnancy to prevent spina bifida. “I remember being at a primary prevention meeting in the early 1990’s ,like this one, to talk about sudden infant death syndrome prevention, which was taking one in 250 children in Tasmania at that time,” she said. “I thought, ‘How are we going to get this done?’ Five years later, it felt so good to be at another meeting, talking about how, after changes in health recommendation, the rate of SIDS had decreased by up to 70% in several countries.”

Future Steps: After reviewing data and hearing from statisticians and clinicians about the feasibility and expense of primary prevention studies, participants agreed to look at three study designs. The next steps are to submit a report based on the summit to a peer reviewed journal, and to begin the process of designing and seeking funding for the proposed prevention trials.

Timothy Coetzee, PhD, chief research officer of the National MS Society, complimented Drs. Hayes, Ponsonby, and colleagues on the “audaciousness” of their efforts. “Can we end MS by something as simple as vitamin D supplementation? This goal is as big as they come, but it fits right into the Society’s bold commitment to do everything possible to free the world of MS.”

 

National MS Society

Related articles

• Vitamin D Supplements Can Help To Prevent Type 1 Diabetes' by 30% (education.com)
• Vitamin D could help combat the effects of aging in eyes (eurekalert.org)
• Natural Cold and Flu Prevention Tips from The Institute for Vibrant Living (prweb.com)

New schizophrenia drug candidates entering prep for first-in-human testing

Vanderbilt research fellow Julie Field prepares to assay novel compounds for activity using a high-throughput screening machine.

The Vanderbilt Center for Neuroscience Drug Discovery announced Dec. 15 that new drug candidates for schizophrenia generated from its ongoing collaboration with Janssen Pharmaceutica, Nev., are now entering the stage of preparation for first-in-human clinical testing.

“This is a major step forward in the evaluation of this approach as a potential treatment for major psychiatric diseases. It could lead to a fundamental advance in the treatment of schizophrenia,” said P. Jeffrey Conn, co-director of the Vanderbilt Center for Neuroscience Drug Discovery.

“This is our goal, to advance patient care,” said Jeff Balser, vice chancellor for health affairs and dean of Vanderbilt University School of Medicine. “What better way to do that than to translate top-notch science and discovery into novel therapeutics.”

The progression of new drug candidates resulting from the agreement with Janssen is the latest evidence that a new collaborative model for drug discovery pioneered at Vanderbilt may help identify and develop innovative candidate drugs for treatment of major brain disorders, said Conn, the Lee E. Limbird Chair in Pharmacology.

The Janssen agreement is especially unique. “It really has been a team effort with dedicated efforts of chemists, biologists, and translational scientists on both sides,” Conn said.

More than 2 million Americans have schizophrenia. Current antipsychotic agents can reduce hallucinations and delusions, he said, but they are less effective in relieving cognitive deficits and other disabling symptoms, including social withdrawal.

Conn, center co-director Craig Lindsley and their colleagues have pioneered the use of “allosteric modulators” to adjust the activity of neurotransmitter receptors in the brain. Rather than activating receptor activity directly, these compounds work like dimmer switches in electrical circuits and induce more subtle changes in receptor function than are seen with traditional receptor agonists.

The target in schizophrenia is a receptor for the neurotransmitter glutamate, called mGluR5, which regulates brain circuits that are disrupted in schizophrenia patients. The drug candidates developed by Vanderbilt and Janssen scientists increase receptor activity and are effective in preclinical models that suggest the possibility of achieving efficacy in schizophrenia patients.

In separate efforts, Vanderbilt recently announced discovery of drug candidates that could relieve symptoms of Parkinson’s disease and fragile X syndrome, the most common genetic cause of autism. For each of these programs, early support by the National Institutes of Health was critical for establishing the basic science underpinnings that encouraged further investment in drug discovery.

“This really does show that this new model (of drug discovery) can work,” Conn said. “It is critical that academic scientists be fully committed to systematically advancing basic research findings to facilitate discovery of novel treatments for unmet clinical needs.”

 

Research news from Vanderbilt.edu

Related articles

• Hospitalization for Schizophrenia (everydayhealth.com)
• Targacept pins hopes on second set of phase 2 trials for schizophrenia, ADHD drug (medcitynews.com)
• The cutting edge of chemistry (life-sciences.blognotions.com)

Spare Parts for Humans: Tissue Engineers Aim for Lab-Grown Limbs, Lungs and More

Watch Spare Parts for Humans: Tissue Engineers Aim for Lab-Grown Limbs, Lungs and More on PBS. See more from PBS NewsHour.

TRANSCRIPTS

JEFFREY BROWN: Next, research breakthroughs that seem almost like science fiction. It's all about growing human tissue and replacing or repairing muscles and, someday, even limbs.

NewsHour science correspondent Miles O'Brien has our story.

 

Be advised: Some of the images are graphic.

MILES O'BRIEN: I am not sure when or why I thought it was a good idea to go for a bike ride on a 100-degree Texas afternoon with a 26-year-old Marine corporal. There I was eating Isaias Hernandez's dirt. No surprise, right? Well, take a look at his right thigh.

CPL. ISAIAS HERNANDEZ, U.S. Marine Corps: It looked like a chicken, like if you would take a bite out of it down to the bone.

MILES O'BRIEN: It happened in Iraq in 2004. He was badly injured in an artillery attack on his convoy.

CPL. ISAIAS HERNANDEZ: They patched it up because they said the other thank option would be amputation because they couldn't just leave my leg on with a hole in it.

DR. STEPHEN BADYLAK, McGowan Institute for Regenerative Medicine: You need people who think quantitatively and qualitatively working together on problems like this.

MILES O'BRIEN: What he did was reach out to this man. Dr. Steve Badylak is deputy director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, where they are in the vanguard of a fast-moving field called tissue engineering. The goal? Grow tissue or even whole organs to repair damaged or diseased human bodies.

Here, they are using pig bladders to help grow human muscle -- that's right, pig bladders. It turns out, they are a good source of a fundamental biological building block known as the extracellular matrix.

DR. STEPHEN BADYLAK: So, the matrix, the extracellular matrix -- we call it ECM -- is a sort of unique collection of structural and functional molecules that we then use as a therapeutic device to tell the body how to heal itself.

MILES O'BRIEN: ECM is like a magnet and a manual for the stem cells inside us. Scientists are not sure why, but the matrix lures those malleable cells and gives them the cues they need to, in this case, morph into muscle.

MILES O'BRIEN: The pillow.

DR. STEPHEN BADYLAK: We call this a powder pillow.

MILES O'BRIEN: The stem cells made their way to a pillow filled with powdered pig bladder matrix implanted in Corporal Hernandez's thigh in 2008. With the help of a lot of hard physical therapy from a very motivated Marine, they became muscle, a lot of muscle.

DR. STEPHEN BADYLAK: We never imagined we were going to get the robust response that we got. Now, he's replaced somewhere between 10 and 15 percent of his muscle mass at that site, but that muscle has gotten so strong that it's something like 50 percent of the strength of the quad.

MILES O'BRIEN: Badylak is starting a larger human trial.

So, using ECM, are you manufacturing body parts?

DR. STEPHEN BADYLAK: We're allowing the body to manufacture. We're setting the stage.

MILES O'BRIEN: Laura Niklason is doing just that in her lab at Yale University. So we can buy parts?

LAURA NIKLASON, Yale University: We have reached the point where we can buy parts. For simple tissues, we can buy parts.

MILES O'BRIEN: Niklason hopes the spare arteries and veins she has grown will be tested in human trials soon, but she is not stopping there. She and her team are growing living, breathing replacement rat lungs that are genetically tailored for a rejection-free transplant, because they are grown from the very cells of the recipient.

LAURA NIKLASON: Otherwise, you would be making a lung that would reject, just like the way lung transplants can reject now. So that's one of the major challenges with engineering a human lung, is we're going to have to learn enough and employ enough stem cell biology so that we can take stem cells from the patient and coax them to become all of the different cell types that we need to make a lung.

MILES O'BRIEN: The key to the coaxing process is our friend the extracellular matrix.

A matrix from a donor rat lung is bathed in cells that are genetically identical to the recipient. The cells marinate in an incubator called a bioreactor for seven days, creating a lung that is a perfect genetic match for the recipient.

If they're not breathing, they don't develop, essentially?

LAURA NIKLASON: Yeah.

MILES O'BRIEN: Unfortunately, the rat lungs she has grown and transplanted so far are short-lived. They fail within hours because of blood clots. Niklason isn't sure why. In fact, there is still a lot she is not sure of.

LAURA NIKLASON: That matrix has an enormous number of cues which we don't yet understand. But it directs the adhesion and the survival of cells within the lung. So, even though we deliver a mixture of cells into the lung, we find that they all go to their proper locations.

MILES O'BRIEN: It will be a long time before scientists will grow a breathing lung or a beating heart that could save a human life, but maybe not as long as you think.

DR. ANTHONY ATALA, Wake Forest Institute for Regenerative Medicine: When we started this, this was really still considered science fiction.

MILES O'BRIEN: Anthony Atala is director of the Wake Forest Institute for Regenerative Medicine. He's been at it for more than two decades. Now, he and his team are working on engineering more than 30 different tissues and organs, bladders and urethras, ears, skin, muscles, human liver tissue, and even a beating heart valve.

DR. ANTHONY ATALA: We know that, naturally, what a heart does is, it beats on its own. So, for us, the concept of recreating this in the laboratory is really nothing more than just recreating what nature already knows how to do.

MILES O'BRIEN: Atala makes it sound easy, but, of course, it is not. Humans do have the ability to regenerate. Our skin, for example, turns over every two weeks or so. But, over time, humans have also evolved to seal up disease and injuries with scars. It's good for keeping us alive after a trauma, but it prevents regeneration.

DR. DAVID GARDINER, University of California, Irvine: Just because we don't regenerate doesn't mean that we can't regenerate. It just means that we don't.

Now, what we have done here is change the information in the cells at the wound-site.

MILES O'BRIEN: Dr. David Gardiner of the University of California, Irvine, is trying to learn how to make humans better regenerators by studying nature's reigning regeneration champ: the salamander.

DR. DAVID GARDINER: When you cut off a salamander's arm, you can cut it off at any level. So, you can cut off fingers, you can cut off at the wrist or the arm or the elbow or the shoulder. And whatever you cut off, that's always what grows back. It doesn't grow back more and it doesn't grow back less.

MILES O'BRIEN: Gardiner wonders how a human who has lost a limb might be able to recover like a salamander.

DR. DAVID GARDINER: We do in fact have intrinsic regenerative abilities, just like the salamander does. It's just like two ends of the spectrum. We're not very good at regenerating complex organ structures like limbs or spinal cords and stuff like that.

MILES O'BRIEN: But there is some promising research on that front as well. Look at this before-and-after video. It's the same paralyzed rat. Its ability to walk greatly improved after cells like these were implanted near its spinal cord injury.

Aileen Anderson is an associate professor at the University of California, Irvine.

AILEEN ANDERSON, University of California, Irvine: What we know is that when we transplant these cells, we can restore the ability of animals with spinal cord injury to step. We can restore their ability to be coordinated.

MILES O'BRIEN: They are called neural stem cells, stem cells that are ideally suited to repair the central nervous system.

So, neural stem cells are more specialized?

AILEEN ANDERSON: Neural stem cells are more specialized. If you picture sort of a tree with embryonic stem cells at the trunk, and all the specialized cells that are relative to different organs like the brain or the spleen or your bone marrow, up in the branches, they become more and more specialized as you ascend.

MILES O'BRIEN: Anderson and her team are working toward clinical trials to inject neural stem cells into humans with spinal cord injuries.

Could these stem cells act like jumper cables? Maybe so.

AILEEN ANDERSON: Our hypothesis, our working plan here is that that restoration of circuitry is what's yielding the recovery of function.

MILES O'BRIEN: But you don't know for sure?

AILEEN ANDERSON: Nobody knows. How -- how many things do you know in science that you know for sure? We think we -- we think we know this because, if we transplant cells and let animals recover to a stable baseline, and then we selectively ablate the human cells that we transplanted, we lose the functional recovery.

MILES O'BRIEN: Francesco Clark is a big believer in the seemingly magical power of stem cells. In 2002, he dove into the shallow end of a pool.

FRANCESCO CLARK: And I was completely paralyzed in the blink of an eye.

MILES O'BRIEN: At first, he could not move a muscle or even breathe on his own. Over time, he has steadily improved, thanks to a tough regimen of physical therapy and, he says, three stem cell treatments he received in China and Germany. They are not yet approved in the U.S.

So, at this point, do you firmly believe there will be a cure for paralysis and that will derive out of stem cells treatments?

FRANCESCO CLARK: Absolutely. Yes, they're no doubt in my mind. I mean, I'm talking, I'm breathing, I'm moving my arms, I'm wiggling around, I'm getting stronger. It's just -- you want to say it's a matter of time, but it's not just time. There's a lot of effort that goes into it.

MILES O'BRIEN: So, how many years before we come back and see you walking around the house here?

FRANCESCO CLARK: I'm pushing for five years.

MILES O'BRIEN: For real?

FRANCESCO CLARK: Yeah.

MILES O'BRIEN: Like any Marine worth his salt, Isaias Hernandez is still pushing as well.

DR. STEPHEN BADYLAK: He's been such a warrior in more ways than one, that he deserves whatever we can give him. So, we're going to do one more surgery on Cpl. Hernandez. We're going to add more matrix and see if we can build more muscle for him and make him even better than he is today. So that's his future.

MILES O'BRIEN: How you feeling?

CPL. ISAIAS HERNANDEZ: Good.

MILES O'BRIEN: His goal for the future? A return to combat.

Why do you want to go back?

CPL. ISAIAS HERNANDEZ: Want to finish up at least a full tour -- if not, then just do everything to the best of my ability.

MILES O'BRIEN: We done yet?

CPL. ISAIAS HERNANDEZ: Depends on how long you want to ride for. Because these trails total, it's about 10 miles.

MILES O'BRIEN: How is the leg?

CPL. ISAIAS HERNANDEZ: Leg's good.

MILES O'BRIEN: Let's do it.

I am living, exhausted proof he already has plenty of ability, thanks in large part to an exploding field of science that may one day make us all live longer and stronger.

JEFFREY BROWN: And it's science Thursday on the NewsHour online. There, we look at images of the giant asteroid Vesta captured by NASA's Dawn spacecraft and beamed back to Earth.

 

PBS NEWHOUR

Related articles

• Blog - "Bio-Assembler" Cultures Cells in 3D Through Magnetic Levitation (technologyreview.com)
• Trillion-frame-per-second video makes speed of light look slow (boingboing.net)
• Amazing Spider-Man Website Launch of the Day (geeks.thedailywh.at)

MS May Take a Different Pathway Than Previously Thought

'Outside-in' disease progression could change approach to diagnosis, treatment, researchers say

 

Multiple sclerosis may begin in the outer layer of the brain and work its way into the deep interior, according to a new study that upends long-held beliefs about the nervous system disease.

The new findings, which could spur changes in the way MS is diagnosed and treated, appear to solidify a theory that's emerged in recent years. This new premise suggests that gray matter, the outer covering of the brain called the cortex, and the fluid that surrounds and cushions it, is where MS originates, not in the bulky white matter that composes most of the brain's core.

It's an "outside-in" process in other words, said study co-author Dr. Claudia Lucchinetti, a professor of neurology at the Mayo Clinic in Rochester, Minn.

"We already recognized before this study that the cortex -- the superficial layer where cells control memory, attention, and other key pathways in the nervous system -- was involved in MS. But most of what we knew came from autopsy studies, from patients who had longstanding disease, 30 to 50 years," said Lucchinetti. The new findings show the cortex is involved early on and may even be the initial target of the disease, she added.

Lucchinetti and her colleagues analyzed brain tissue of early MS patients obtained through biopsies. The tissue was primarily white matter, but about one-fourth of the biopsies (138 of 563 patient screenings) also included tiny fragments of cortex. The scientists used that tissue as the focus of their study.

The cortical tissues were viewed on a microscopic level. "The early lesions were highly inflammatory," said Lucchinetti, whose research is published in the Dec. 8 issue of the New England Journal of Medicine.

The authors also noted that inflammation was also present in the meninges, the protective membranes that cover the surface of the brain and spinal cord, and was strongly associated with inflammation in the cortex tissue.

About 400,000 Americans have MS, according to the National Multiple Sclerosis Society. Its cause is unknown, but it is believed to occur when the body's immune system chips away at the protective myelin sheath, a fatty insulator that covers nerves, and it can be debilitating. Symptoms can include weakness and numbness, paralysis, poor vision, fatigue, dizziness, and tremor. Its severity varies widely in patients, said Lucchinetti.

Lucchinetti said if scientists can understand the genesis of the disease, better diagnostic procedures and treatments could be developed.

"The findings are provocative," said Dr. Peter Calabresi, professor of neurology and director of the MS Center at Johns Hopkins Hospital, who wrote an accompanying editorial.

"It's an exciting study. For many years we thought MS was predominantly a disease of the white matter. More recently people have found there are some changes in the gray matter. This is the first time that anyone has definitively shown there's extensive inflammation in the gray matter early on in the disease," said Calabresi.

Calabresi likens the findings to leaves on a tree. "Everyone thought the attack was on the leaves, the white matter, but now people think it's more likely the trunk," he said.

Should patients get excited?

Dr. Jerome Graber, an assistant professor of neurology at Albert Einstein College of Medicine in the Bronx, N.Y., said it's a good study, but suggests no immediate clinical benefits. "My answer to my patients is that it doesn't have an immediate implication for them yet. I have no new treatment for you because of this study. But I think it opens a lot of doors for researchers to ask a whole new set of questions," he said. And the link with the meninges is also intriguing, he said.

Calabresi agreed it offers hope. "I think it gives us a lot of hope," he said. "It gives us yet one more tool to follow the disease. There's a mysterious aspect to MS. It's hard to quantify. But now we know gray matter is definitely involved, and we can track it and see if a therapy is working or not, and if not, move on to the next therapy."

Ultimately, this research "will allow us to understand [MS] better and track and treat it better," he said.

 

Medline Plus

Related articles

• Mayo Clinic collaboration finds multiple sclerosis often starts in brain's outer layers (eurekalert.org)
• Multiple sclerosis often starts in brain's outer layers: study (medicalxpress.com)

Neurons grown from skin cells may hold clues to autism

Potential clues to how autism miswires the brain are emerging from a study of a rare, purely genetic form of the disorders that affects fewer than 20 people worldwide. Using cutting-edge “disease-in a-dish” technology, researchers funded by the National Institutes of Health have grown patients' skin cells into neurons to discover what goes wrong in the brain in Timothy Syndrome. Affected children often show symptoms of autism spectrum disorders along with a constellation of physical problems.

Abnormalities included changes in the composition of cells in the cortex, the largest brain structure in humans, and of neurons that secrete two key chemical messengers. Neurons that make long-distance connections between the brain’s hemispheres tended to be in short supply.

Most patients with Timothy Syndrome meet diagnostic criteria for an autism spectrum disorder. Yet, unlike most cases of autism, Timothy syndrome is known to be caused by a single genetic mutation.

"Studying the consequences of a single mutation, compared to multiple genes with small effects, vastly simplifies the task of pinpointing causal mechanisms," explained Ricardo Dolmetsch, Ph.D., of Stanford University, a National Institute of Mental Health (NIMH) grantee who led the study. His work was partially funded by a NIH Director’s Pioneer Award.

Dolmetsch, and colleagues, report on their findings Nov. 27, 2011 in the journal Nature Medicine.

"Unlike animal research, the cutting-edge technology employed in this study makes it possible to pinpoint molecular defects in a patient's own brain cells," said NIMH Director Thomas R. Insel, M.D. "It also offers a way to screen more rapidly for medications that act on the disordered process."

Prior to the current study, researchers knew that Timothy syndrome is caused by a tiny glitch in the gene that codes for a calcium channel protein in cell membranes. The mutation results in too much calcium entering cells, causing a tell-tale set of abnormalities throughout the body. Proper functioning of the calcium channel is known to be particularly critical for proper heart rhythm — many patients die in childhood of arrhythmias — but its role in brain cells was less well understood.

To learn more, Dolmetsch and colleagues used a new technology called induced pluripotent stem cells (iPSCs). They first converted skin cells from Timothy Syndrome patients into stem cells and then coaxed these to differentiate into neurons.

 
Representitive iPSC-derived neurons from Timothy Syndrome patient (bottom) shows increased numbers of neurons that produce the chemical messengers norepinephrine and dopamine, compared to those from a control subject (top). Source: Ricardo Dolmetsch, Ph.D., Stanford University

"Remarkable reproducibility" observed across multiple iPSC lines and individuals confirmed that the technique can reveal defects in neuronal differentiation — such as whether cells assume the correct identity as the brain gets wired-up in early development, said the researchers. Compared to those from controls, fewer neurons from Timothy Syndrome patients became neurons of the lower layers of the cortex and more became upper layer neurons. The lower layer cells that remained were more likely to be the kind that project to areas below the cortex. In contrast, there were fewer-than-normal neurons equipped to form a structure, called the corpus callosum, which makes possible communications between the left and right hemispheres.

Many of these defects were also seen in parallel studies of mice with the same genetic mutation found in Timothy syndrome patients. This supports the link between the mutation and the developmental abnormalities.

Several genes previously implicated in autism were among hundreds found to be expressed abnormally in Timothy Syndrome neurons. Excess cellular calcium levels also caused an overproduction of neurons that make key chemical messengers. Timothy Syndrome neurons secreted 3.5 times more norepinephrine and 2.3 times more dopamine than control neurons. Addition of a drug that blocks the calcium channel reversed the abnormalities in cultured neurons, reducing the proportion of catecholamine-secreting cells by 68 percent.

The findings in Timothy Syndrome patient iPSCs follow those in Rett Syndrome, another single gene disorder that often includes autism-like symptoms. About a year ago, Alysson Muotri, Ph.D., and colleagues at University of California, San Diego, reported deficits in the protrusions of neurons, called spines, that help form connections, or synapses. The Dolmetsch team’s discovery of earlier (neuronal fate) and later (altered connectivity) defects suggest that disorders on the autism spectrum affect multiple stages in early brain development.

Forebrain of a mouse genetically engineered to express the mutated gene that causes Timothy Syndrome (TS) shows fewer neurons contributing to a brain structure responsible for long-distance communications between the left and right hemispheres, called the corpus callosum, compared to the same structure in a control animal (Ctrl). Human iPSCs from TS patients showed a similar reduction.Source: Ricardo Dolmetsch, Ph.D., Stanford University

 

"Most of these abnormalities are consistent with other emerging evidence that ASDs arise from defects in connectivity between cortex areas and show decreased size of the corpus callosum," said Dolmetsch. "Our study reveals how these might be traceable to specific mechanisms set in motion by poor regulation of cellular calcium. It also demonstrates that neurons derived from iPSCs can be used to identify the cellular basis of a neurodevelopmental disorder."

The mechanisms identified in this study may become potential targets for developing new therapies for Timothy Syndrome and may also provide insights into the neural basis of deficits in other forms of autism, said Dolmetsch.

The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure.

 

 NIMH website.

 

Related articles

• 67% More Prefrontal Brain Neurons In Children With Autism (medicalnewstoday.com)
• Skin cells may hold clues to autism (scienceblog.com)
• Scientists identify defect in brain cell channel that may cause autism-like syndrome (eurekalert.org)

Autoimmune drugs don’t boost infection risk

Effective injectable biologic drugs used to treat autoimmune disorders such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and psoriasis do not increase the risk of hospitalization for serious infection compared with the use of other non-biologic medications, according to a Vanderbilt study published in the Journal of the American Medical Association (JAMA).

A class of drugs known as tumor necrosis factor (TNF)-α antagonists has revolutionized the treatment of autoimmune disorders, which occur when the body’s immune system attacks healthy cells and tissue. They are known as biologic medications because their substances occur naturally in animals and humans. They work by blocking the TNF-α molecule.

But concerns about their safety have remained because they suppress the immune system. Previous studies have reported serious infections in users of TNF-α antagonists compared with placebo, but whether that risk is greater than with non-biologic medications had previously been unclear.

Carlos Grijalva, assistant professor of preventive medicine, and colleagues compared the risk of serious infections for both types of medications by combining data from four major U.S. databases (1998-2007) and comparing the occurrence of hospitalizations for infections among patients initiating TNF-α antagonists or non-biologic regimens.

Data analyses indicated that hospitalization rates for serious infection were not significantly different between the TNF-α antagonists overall and the comparator non-biologic regimens for RA, IBD, and psoriasis, psoriatic arthritis or ankylosing spondylitis.

“I think it should be reassuring for patients and providers that in this large study we observed that these biologic medications did not increase the risk of serious infections when compared with other non-biologic treatments,” Grijalva said.

Patients and providers can evaluate this and other available information to make informed decisions about the best options for their treatment.”

Study authors did report that, among patients with RA, the medication infliximab was associated with a significant increase in serious infections compared with the drugs etanercept, adalimumab and other non-biologic medications.

A multi-institution collaboration, called the Safety Assessment of Biologic Therapies, or SABER, was established for the study and included Vanderbilt University, the University of Alabama at Birmingham, Harvard University, Kaiser Permanente Northern California, Oregon Health and Sciences University, University of Pennsylvania, the Food and Drug Administration and the Agency for Healthcare Research and Quality.

The study was funded by the FDA, AHRQ, Department of Health and Human Services and the National Institutes of Health.

 

Vanderbilt.edu

Related articles

• MS Patients Must Not Use TNF-Inhibitor Drugs (brassandivory.org)
• Psoriasis, RA drugs don't raise infection risk (cnn.com)
• Some Rheumatoid Arthritis Drugs Not Linked To Serious Infections (medicalnewstoday.com)
• new biologic side effects warning (cupsquietlybeingfilled.wordpress.com)
• Rheumatoid Arthritis Drugs May Have Small Skin Cancer Risk (webmd.com)
• Combination Therapy for Rheumatoid Arthritis (webmd.com)

New Approach to Re-Educate the Immune System Could Help In Rheumatoid Arthritis Treatment

A vaccine designed to re-educate the immune system has been shown to be safe and feasible in the treatment of rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Chicago.

 

A vaccine designed to re-educate the immune system has been shown to be safe and feasible in the treatment of rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Chicago.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

"RA is caused by an aberrant response that can be triggered by disease-specific antigens, or proteins," says lead investigator Ranjeny Thomas, MBBS MD; professor of rheumatology at The University of Queensland Diamantina Institute. "Current treatments attempt to reduce the joint destruction associated with this disease by targeting the inflammation that is a consequence of this immune response. However, non-specific suppression of inflammation may increase infection, and drugs may be toxic to vital organs."

Dr. Thomas' team recently completed a study looking at the feasibility and safety of using a vaccine, called Rheumavax®, to reduce the way a person's immune system reacts towards the disease antigens thought to cause RA.

"Approximately 70 to 80 percent of RA patients make antibodies towards RA-specific antigens called citrullinated peptides, which are identifiable with a blood test," explains Dr. Thomas. "While antigen-specific immune tolerance is a major goal for RA prevention and treatment, early trials failed to show a response, and the strategy was abandoned when biologic therapy was spectacularly successful. We reasoned the problem might be solved if the dendritic cells that normally educate the immune system towards these antigens were modified with a drug that would promote immune tolerance."

And, with that thought in mind, Dr. Thomas' team designed Rheumavax using drug-modified dendritic cells (generated from a person's own blood) and citrullinated peptide antigens, to suppress specific RA immune reactivity (or restore immune tolerance) - leaving broader immunity towards infections intact.

Once the vaccine was developed, the researchers identified 29 people with RA (predominately female with an average age of 56) who had suffered from the disease for an average of 5.5 years, and who were treated with at least one disease modifying anti-rheumatic drug (commonly called DMARDs).

These participants were placed into three groups. The first group of nine received 1 million Rheumavax dendritic cells, the second group of nine received 5 million, and the third (the control group) of 11 received their usual DMARDS. The cells were given once, through an injection into the thigh.

Participants were evaluated monthly for six months, and the researchers looked for safety issues, immune tolerance and changes in RA activity.

Overall, Rheumavax was well tolerated at both dosages and did not cause any skin reactions, allergic reactions, infections, or immediate disease flares. Some side effects were noted, but were all minor. These included headache, anemia, decrease in white blood cells, and altered liver function tests.

Additionally, the researchers found that those participants with lower levels of disease activity before receiving Rheumavax continued to have low disease activity, and improvements occurred after receiving Rheumavax in patients who started with higher levels of disease activity. Participants receiving Rheumavax also had improvements in blood inflammatory markers and glucose tolerance.

"This study shows that a new approach to re-educate the immune system towards RA-specific antigens using dendritic cells can be safe, says Dr. Thomas. "Similar strategies could now be developed and tested for RA prevention and treatment using this concept."

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.rheumatology.org/education.

SF.GATE

Related articles

• Psoriasis, RA drugs don't raise infection risk (cnn.com)
• Could Low Expectations By Rheumatoid Arthritis Patients Be Holding Them Back After Knee Replacement Surgery? (medicalnewstoday.com)
• Young women with rheumatoid arthritis at more risk for broken bones (medicalxpress.com)

CBS MORNING -Bionics: Melding man with machine

 

 

Step by step, bionic engineers are transforming lives in ways that barely could have been imagined until recently with researchers perfecting ways to make the disabled walk and even the blind see. Barry Petersen reports.

 

CBS NEWS

Related articles

• Robotic Arm Moved Just By Thinking About It. (worldnewsrecord.wordpress.com)
• Motorola Droid Bionic Review (pocketnow.com)
• Paralyzed man uses mind-powered robot arm to touch (sfgate.com)

Cracking The Conundrum Of Chronic Fatigue Syndrome

Nearly three decades have passed since the debate began about a series of symptoms that have come to be known as chronic fatigue syndrome. Its cause is still unknown, but over the years, researchers have identified various brain, immune system and energy metabolism irregularities involved. Some patients describe the syndrome as feeling like an "unrelenting, unremitting flu."

Doctors say some treatments can help. Arthur Barsky, a psychiatrist at Brigham and Women's Hospital in Boston and a professor at Harvard Medical School, says patients need to change how they experience symptoms — typically pain, insomnia and anxiety. When patients adopt a more positive attitude, Barsky points out, it often translates into greater confidence and more energy.

A study published this year in the Lancet found that a form of talk therapy, as well as exercise, offered relief for some patients. Researchers from the United Kingdom looked at cognitive behavior therapy, or CBT.

In the study, over 600 patients with chronic fatigue syndrome were assigned to different treatments. All of them received medical care for symptoms like pain, insomnia or anxiety.

One group got counseled about how to pace activities. Another took part in an exercise program. And a third received the cognitive behavioral talk therapy. The therapy and the exercise group improved the most, reporting less fatigue, insomnia and anxiety.

Barsky says his patients do best when cognitive behavior therapy is also combined with gradually increased exercise. "People need to begin to push themselves in the face of their fatigue, because if you don't, you become deconditioned and you get caught in a cycle which ... makes fatigue worse," says Barsky.

But he cautions against overdoing it. People should start with mild, gentle exercise like clearing the table, doing the dishes, or taking the dog for a short walk. Then, slowly build up to longer and more frequent walks, he says.

Lucinda Bateman is a doctor at the Fatigue Consultation Clinic in Salt Lake City who specializes in chronic fatigue syndrome.

She's skeptical about the Lancet study, pointing out that patients improved only moderately, and not much more than those who were counseled about pacing themselves. Bateman suggests her patients pace themselves, and try to do only as many activities as they can manage.

She says some patients get caught in a "push and crash" cycle. When symptoms abate and they feel better, they may go all out, exercising, doing errands and socializing. But soon that level of activity often comes to a crashing end and patients can relapse dramatically, even becoming bedridden for several days or longer.

Bateman takes also issue with CBT's implication that chronic fatigue syndrome is psychosomatic. We still don't know what exactly causes the syndrome. And, like most professionals who treat patients, Bateman eagerly awaits the day when science can finally pinpoint its cause.

 

npr/healthblog

Related articles

• Guest Blogger: James from Chronic Fatigue Treatments (livinglifewithraandfms.wordpress.com)
• An apology to patients with chronic fatigue syndrome (kevinmd.com)
• Iraq & Afghanistan "safer than Chronic Fatigue researching" (getintomedicineuk.com)

Genes play greater role in heart attacks than stroke, researchers say

Study Highlights:

• People are more likely to inherit a predisposition to heart attack than to stroke.
• The finding supports earlier research that showed genes influencing stroke risk are largely those involved in regulating blood pressure.
• The researchers say heart and stroke risk should be assessed separately in healthy people.

 

DALLAS TX,

People are significantly more likely to inherit a predisposition to heart attack than to stroke, according to research reported in Circulation: Cardiovascular Genetics, an American Heart Association journal.

The study results have implications for better understanding the genetics of stroke and suggest the need for separate risk assessment models for the two conditions. 

“We found that the association between one of your parents having a heart attack and you having a heart attack was a lot stronger than the association between your parent having a stroke and you having a stroke,” said senior author Peter M. Rothwell, M.D., Ph.D., professor of clinical neurology at Oxford University in England. “That suggests the susceptibility to stroke is less strongly inherited than the susceptibility to heart attack.”

 A second analysis, which included patients’ siblings as well as parents, yielded the same result:

Family history proved a stronger risk predictor for heart attack than for stroke.

Rothwell and his colleagues conducted the study to clarify and confirm evidence suggesting a great difference in genetic predisposition between heart attacks and strokes.

“We had found previously that much of the heritability of stroke is related to the genetics of high blood pressure, which doesn’t seem to be the case for heart attack,”

Rothwell said. Hypertension appears to be closely related with stroke rather than heart attack, which is why a family history of hypertension is related to a higher risk of stroke.

In the report published today, all patients were enrolled in the ongoing Oxford Vascular Study. OXVASC, as the study is known, that began in 2002 to study strokes, heart attacks and other acute vascular events in a part of Oxfordshire County where more than 91,000 people are served by one hospital. Previous analyses in the same population conducted by lead author, Amitava Banerjee MPH PhD, have shown the particular importance of family history in mother-daughter transmission in both heart attacks and stroke. “Family history of heart attacks and family history of strokes have rarely been studied in the same population,” Banerjee said. 

The researchers used data from 906 patients (604 men) with acute heart ailments and 1,015 patients (484 men) who suffered acute cerebral events. Among the study’s findings:

• In the heart patients, 30 percent had one parent who’d had a heart attack, 21 percent had at least one sibling who had suffered a heart attack. Seven percent had two or more siblings who had heart attacks and 5 percent had two parents with heart attack.
• Among the patients with a stroke or transient ischemic attacks (TIAs, often called a mini-strokes or warning strokes), 21 percent had one parent who had a stroke, and 2 percent had two parents with stroke. Eight percent had at least one sibling with a stroke and 1.4 percent had at least two siblings with stroke.
• The risk of a sibling developing acute heart problems was similar for those with heart attack or stroke.
• The risk for an acute cardiac event was six times greater if both parents had suffered a heart attack and one-and-a-half times greater if one parent had a heart attack. In contrast, the likelihood of stroke did not change significantly with parents’ stroke history.

The findings, if confirmed by additional studies, hold two significant implications, Rothwell said.

“First, the way physicians predict the odds of a healthy person suffering a heart attack or stroke needs refining,” he said. “Currently, most risk models lump a patient’s family history of stroke and heart attack together. We probably should model family history of stroke and heart attack separately in the future.”

The new data also indicated that using the same criteria to predict both medical events overestimate the risk of stroke, he added.

“The knowledge of genetic factors in stroke lags behind that in coronary artery disease,” Rothwell said. The discovery that genes play a significantly smaller role in stroke could mean that genetic studies of stroke may not be critical to the field, he added.

 

American Heart Association

 

Piercing a Tongue, in the Name of Mobility

Martin Mireles is part of a clinical trial at Northwestern's medical school.

 

CHICAGO —

Martin Mireles says his mother was not happy with his tongue piercing: It didn’t fit his image as a former church youth leader.

But as Mr. Mireles told her, it was for research. Paralyzed from a spinal cord injury since he was shot in the neck almost two decades ago, he was recently fitted with a magnetic stud that allows him to steer his wheelchair with his tongue.

Now he is helping researchers at the Northwestern University School of Medicine here in a clinical trial of the technology, being financed with almost $1 million in federal stimulus funds.

Mr. Mireles, 37, tested the equipment one recent afternoon by guiding a wheelchair through an obstacle course lined with trash cans. Mouth closed, he shifted the magnet to travel forward and backward, left and right.

The study was one of about 200 projects selected from more than 20,000 applicants.

“There was a ‘wow’ factor here,” said Naomi Kleitman, a program director at the National Institutes of Health and an expert on spinal cord injury research. “This is kind of a cool idea. The question is: Will it work well enough not to just be cool, but to be practical too?”

A quarter-million Americans have severe spinal cord injuries, and experts estimate that there are about 10,000 new injuries each year. Millions more have some form of paralysis from an array of conditions, including stroke, multiple sclerosis and cerebral palsy.

Wheelchair users do have several options now, including the “sip and puff” technology, used by the actor Christopher Reeve before his death in 2004, in which the chair is steered by breathing through a straw.

But Maysam Ghovanloo, assistant professor of electrical and computer engineering at the Georgia Institute of Technology, wanted to create a technology that would be more aesthetically pleasing — without a straw obscuring the face — and more intuitive for users, with better control and greater flexibility.

After working on the tongue drive system for about five years, Dr. Ghovanloo is now conducting the clinical trials with Northwestern, the Rehabilitation Institute of Chicago and the Shepherd Center in Atlanta.

To operate the system, the user wears a headset with sensors that pick up magnetic signals from the tongue ring. Moving the tongue to the mouth’s upper left corner, for instance, moves the wheelchair forward. (The researchers hope that in the future, touching each tooth could signal a different command, from turning on the television to answering the phone to opening a door.)

Researchers decided to use the tongue because they wanted to take advantage of some of the functions a severely disabled person still had. The tongue does not tire easily, they said, and it is not usually affected by a spinal cord injury because it is directly connected to the brain through a cranial nerve.

At first they just glued the magnet to the user’s tongue, but it often fell off after a few hours. The idea for the piercing came from Dr. Anne Laumann, an associate professor of dermatology at Northwestern who had studied body art.

Ann Carias, a nondisabled volunteer who had her tongue pierced for the study, said it hurt for a few days but healed faster than she expected. When she tested the wheelchair, she said it became easier to steer the more she used it.

Ms. Carias, a 30-year-old Ph.D. student who has several other piercings and large tattoos, said she sometimes felt judged because of her piercings. She thinks the technology will give disabled people more freedom — and could have a side benefit for others as well.

“I think it’s great that something taboo can be used for therapeutic reasons,” she said.

 

NY Times

Studies are a blow to thoes with chronic fatigue syndrome

In a blow to patients with chronic fatigue syndrome, two new studies published on Tuesday raised serious doubts about earlier reports that the disabling disease is linked to infection with XMRV, a poorly understood retrovirus.

The new papers were posted online in the journal Science, which in October 2009 published the initial research linking XMRV to chronic fatigue syndrome. In an “editorial expression of concern” accompanying the two new studies, Bruce Alberts, editor in chief of the journal, declared that the earlier finding “is now seriously in question” and was most likely due to laboratory contamination.

Based on those earlier findings, some people with chronic fatigue syndrome tried to obtain access to antiretroviral drugs used to treat H.I.V., which had been shown in laboratory studies to inhibit the replication of XMRV.

But in one of the two new studies, researchers found no trace of XMRV or related viruses in the blood of 43 patients who had previously tested positive for XMRV. In the second study, scientists reported evidence that XMRV was likely a recombination of two mouse leukemia viruses created accidentally in laboratory experiments.

The new studies are the latest in a series of disappointments for people struggling with chronic fatigue syndrome. Other researchers have been unable to duplicate the original findings implicating XMRV, although none of their studies fully replicated the methods of the original research from the Cleveland Clinic, the National Cancer Institute and the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nev.

Dr. Vincent Racaniello, a microbiology professor at Columbia University, said in an interview that it now appeared unlikely that XMRV infection is a cause of chronic fatigue syndrome. But it also would be wrong to conclude that chronic fatigue syndrome is not an infectious disease, he added.

“These patients have a lot of signs of hyper-immune activation, with their immune systems firing almost constantly,” he said.

Dr. Jay Levy, a professor of medicine at the University of California, San Francisco, and the senior author of one of the new studies, said he nonetheless believed that many or most people with chronic fatigue syndrome are suffering from a disease initiated by one or more viruses.

Many of the disease’s symptoms are likely caused by the immune systems’ response to an infection, rather than to the pathogens themselves, he said.

“The immune system pours out its toxins to stop this agent, and then the immune system doesn’t calm down,” he said, adding that environmental toxins could also play a role in the illness.

Last week, the editors of Science asked the authors of the original research if they would retract their paper in view of the new findings about to be published. The senior author, Dr. Judy Mikovits, research director at the Whittemore Peterson Institute, responded that such a step was “premature” and that she knew of other investigators planning to publish research backing the original findings.

Some patients reacted angrily to the news that Science had asked for a retraction. “The patient community is shocked,” Rivka Solomon, a largely homebound Boston-area writer with chronic fatigue syndrome, said in an e-mail. “Most of us feel that the scientific inquiry necessary to bring this to conclusion has not yet been played out.”

Ms. Solomon recently organized small demonstrations in Washington, D.C., and San Francisco to focus attention on the small amount of financing the government has allocated to the disease in recent years. If the XMRV association does not pan out, she wrote, patients like her “worry that we will once again be abandoned.”

The government is supporting additional studies to determine whether XMRV plays any role in chronic fatigue syndrome at all. The retrovirus had also been linked to prostate cancer, an association also challenged by the research published on Tuesday.

NY TIMES

Autism Blurs Brain Tissue’s Distinctiveness

Erodes Molecular Identities In Cortex – NIH-funded Study

Autism blurs the molecular differences that normally distinguish different brain regions, a new study suggests. Among more than 500 genes that are normally expressed at significantly different levels in the front versus the lower middle part of the brain's outer mantle, or cortex, only 8 showed such differences in brains of people with autism, say researchers funded, in part, by the National Institutes of Health.

"Such blurring of normally differentiated brain tissue suggests strikingly less specialization across these brain areas in people with autism" explained Daniel Geschwind, M.D., Ph.D., of the University of California Los Angeles, a grantee of the NIH's National Institute of Mental Health. "It likely reflects a defect in the pattern of early brain development."

He and his colleagues publish their study in post-mortem brains of people with the disorder online May 26, 2011 in the journal Nature.

In early development, different mixes of genes turn on in different parts of the brain to create distinct tissues that perform specialized functions. The new study suggests that the pattern regulating this gene expression goes awry in the cortex in autism, impairing key brain functions.

"This study provides the first evidence of a common signature for the seemingly disparate molecular abnormalities seen in autism," said NIMH director Thomas R. Insel, M.D. "It also points to a pathway-based framework for understanding causes of other brain disorders stemming from similar molecular roots, such as schizophrenia and ADHD."

In an earlier study, the researchers showed that genes that turn on and off together at the same time hold clues to the brain's molecular instructions. These "modules" of co-expressed genes can reveal genetic co-conspirators in human illness, through what Geschwind and colleagues call "guilt by association." A gene is suspect if its expression waxes and wanes in-sync with others in an illness-linked module.

Using this strategy, the researchers first looked for gene expression abnormalities in brain areas implicated in autism — genes expressed at levels different than in brains of healthy people. They found 444 such differently expressed genes in the cortex of postmortem brains of people with autism, compared to only 2 in the cerebellum. So they focused on the cortex.

Most of the same genes turned out to be differently expressed in the frontal cortex as in the temporal cortex (lower middle) of autistic brains. Of these, genes involved in synapses, the connections between neurons, tended to be under-expressed, when compared with healthy brains. Genes involved in immune and inflammatory responses tended to be over-expressed. Significantly, the same pattern held in a separate sample of brains.

In both autistic and healthy control brains, modules of co-expressed genes related to specific cell types and biological functions. Yet, none of the modules of co-expressed genes in autistic brains showed any of the differences in expression levels normally seen between the frontal and temporal cortex. This suggested that the normal molecular distinctions — the tissue differences — between these regions are nearly erased in the brain disorder. Strikingly, among 174 genes expressed at different levels between the two regions in two healthy control brains, none were expressed at different levels in brains of people with autism.

An analysis of gene networks revealed two key modules of co-expressed genes highly correlated with autism.

One module was made up of genes in a brain pathway involved in neuron and synapse development, which were under-expressed in autism. Many of these genes were also implicated in autism in previous, genome-wide studies. So several different lines of evidence now converge, pointing to genes in this M12 module (see picture below) as genetic causes of autism.

A second module of co-expressed genes (called M16), related to astrocytes and glial cells, was over-expressed in autism. These were determined not to be genetic causes of the illness, but likely related to secondary inflammatory, immune, or possible environmental factors involved in autism.

This newfound ability to see genes in the context of their positions in these modules, or pathways, provides hints about how they might work to produce illness, according to Geschwind and colleagues.

Follow-up studies should explore whether the observed abnormalities in the patterning of gene expression might also extend to other parts of the brain in autism, say the researchers.

A module of co-expressed genes that code for neurons and their connections tend to be under-expressed in many individuals with autism (red), compared to controls (gray).

Reference

Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, Mill J, Cantor R, Blencowe BJ, Geschwind DH. Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology. Nature. 2011 June 15.

NIMH

Bacteria 'linked' to Parkinson's disease

The bacteria responsible for stomach ulcers have been linked to Parkinson's disease, according to researchers in the US.

 

Could this bacterium cause Parkinson's disease?

 

Mice infected with Helicobacter pylori went onto develop Parkinson's like symptoms.

The study, presented at a meeting of the American Society for Microbiology, argues that infection could play "a significant role".

The charity Parkinson's UK said the results should be treated with caution.

Parkinson's disease affects the brain and results in slow movements and a tremor.

Middle-aged mice, the equivalent of being between 55 and 65 in humans, were infected. Six months later they showed symptoms related to Parkinson's, such as reduced movement and decreased levels of a chemical, dopamine, in the brain.

These changes were not noticed in younger mice.

 

Toxic

Dr Traci Testerman, from the Louisiana State University Health Sciences Center, said: "Our findings suggest that H. pylori infection could play a significant role in the development of Parkinson's disease in humans.

"The results were far more dramatic in aged mice than in young mice, demonstrating that normal ageing increases susceptibility to Parkinsonian changes in mice, as is seen in humans."

The researchers believe the bacteria are producing chemicals which are toxic to the brain.

They said H. pylori was able to "steal" cholesterol from the body and process it by adding a sugar group.

 

The bacteria responsible for stomach ulcers may have a role in Parkinson's say researchers.

 

Dr Testerman said this new chemical was almost identical to one found in seeds from the cycad plant, which had been shown to trigger a Parkinson's-like disease among people in Guam.

 

She told the BBC: "H. pylori eradication in late stage Parkinson's disease is unlikely to result in significant improvement.

 

"Certain neurons are killed before symptoms begin, and more are killed as the disease progresses. Those neurons will not grow back."

 

Dr Kieran Breen, director of research at Parkinson's UK, said: "We believe Parkinson's is most likely caused by a combination of environmental factors together with an individual's genetic susceptibility to developing the condition.

 

He said there was some evidence that bacteria can prevent the main drug to treat Parkinson's, levodopa, being absorbed, but there was no strong evidence that people who have H. pylori in their gut are actually more likely to develop Parkinson's.

 

He added: "The current study is interesting and suggests that the bacteria may release a toxin that could kill nerve cells.

 

"However, the results should be treated with caution. The research was carried out in mice that were infected with relatively high doses of the bacterium or its extract.

 

"While they developed movement problems, we don't know whether this was actually due to the death of nerve cells. Further research needs to be carried out".

 

LINKS:

BBC NEWS

BBC NEWS/PARKINSONS

 

Ecstasy associated with chronic change in brain function

Ecstasy – the illegal “rave” drug that produces feelings of euphoria and emotional warmth – has been in the news recently as a potential therapeutic. Clinical trials are testing Ecstasy in the treatment of post-traumatic stress disorder.

But headlines like one in Time magazine’s health section in February – “Ecstasy as therapy: have some of its negative effects been overblown?” – concern Ronald Cowan, associate professor of Psychiatry.

His team reports in the May issue of Neuropsychopharmacology that recreational Ecstasy use is associated with a chronic change in brain function.

“There’s tension in the fields of psychiatry and psychotherapy between those who think Ecstasy could be a valuable therapeutic that’s not being tested because of overblown fears, and those who are concerned about the drug’s potentially harmful effects,” Cowan said.

“We’re not on one side or the other; we’re just trying to find out what’s going on in the brain – is there any evidence for long-lasting changes in the brain?”

The message in news reports needs to be accurate, Cowan said. His team’s studies suggest that the current message should be: “If you use Ecstasy recreationally, the more you use, the more brain changes you get.”

Cowan and his colleagues examined brain activation during visual stimulation, using functional magnetic resonance imaging (MRI), in subjects who had previously used Ecstasy (but not in the two weeks prior to imaging) and in subjects who had not previously used Ecstasy.

They found increased brain activation in three brain areas associated with visual processing in Ecstasy users with the highest lifetime exposure to the drug. The findings were consistent with the investigators’ predictions based on results from animal models: that Ecstasy use is associated with a loss of serotonin signaling, which leads to hyper-excitability (increased activation) in the brain.

The hyper-excitability suggests a loss in brain efficiency, Cowan said, “meaning that it takes more brain area to process information or perform a task.”

The investigators found that this shift in brain excitability did not return to normal in subjects who had not used Ecstasy in more than a year.

“We think this shift in cortical excitability may be chronic, long-lasting, and even permanent, which is a real worry,” Cowan said, noting that the Ecstasy users in the study are young (18 to 35 years old). “The question is what will happen to their brains as they age over the next 60 years.”

Cowan said that the pattern of hyper-excitability is similar to that observed in fMRI studies of individuals at risk for, or with early, Alzheimer’s disease.

“I’m not saying that these people are at increased risk for dementia, but that there’s a loss of brain efficiency in both recreational Ecstasy use and early Alzheimer’s.”

The findings suggest that brain hyper-excitability (increased activation in fMRI scans) may be a useful biomarker for Ecstasy-induced neurotoxicity, which the investigators will continue to study.

“Our goal is to be able to let people know whether or not the drug is causing long-term brain damage,” Cowan said. “That’s really critical because millions of people are using it.”

The 2009 National Survey on Drug Use and Health estimated that 14.2 million individuals 12 years or older in the United States had used Ecstasy in their lifetime; 760,000 people had used Ecstasy in the month prior to being surveyed.

Cowan is also interested in determining the doses of Ecstasy that are toxic, and whether there are genetic vulnerabilities to toxicity. If clinical trials show that the drug has therapeutic benefits, it’s critical to know the risks, he said.

The research was supported by the National Science Foundation, the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Center for Research Resources.

Vanderbilt

 

Related articles

• Long-term users of ecstasy risk structural brain damage (eurekalert.org)
• Ecstasy associated with chronic change in brain function (sciencedaily.com)
• Long-term ecstasy use 'raises risk of brain damage and Alzheimer's' (guardian.co.uk)

There Is No 'Autism Epidemic': UK Study

 

Is autism a growing epidemic or not? Recent reports have suggested that autism is on the rise, but a new study from the U.K. finds that the prevalence of this developmental disorder has remained stable. It may be that doctors are diagnosing it more often in young people -- not that it's actually happening more.

Researchers performed clinical assessments of 618 adults and found that nearly 1 percent of Britons over age 16 suffered from autism -- meaning the adult rate is no higher than that seen among children in the U.K.

"If the rate of autism is actually increasing rapidly, you'd expect rates to be much lower in older adults, but we didn't find that," says Dr. Traolach Brugha, lead author on the study and psychiatrist at the University of Leicester, U.K. "We found similar rates at 16 up to the 70s and 80s. That suggests that the number of people developing the condition have not changed over the last seventy or eighty years."

Though this study deals with the U.K. population, these findings call into questions whether the much-discussed "autism epidemic" in the U.S. is a real phenomenon.

"It has never been fully clear whether the much increased rate of autism over the past few decades is due to increased recognition…or whether there has been a genuine increase. This study suggests that there is no true increase," says Dr. Shlomo Shinnar, professor of neurology and pediatrics at Montefiore Medical Center in New York.

Because the U.K. and the U.S. have similar rates of autism in children (about 1 percent), these U.K. findings speak to the autism debate in the states as well, says Shinnar. "The fact that similar rates of 1 percent are being seen in the adult population when screened is a strong indication that these results are highly relevant to the U.S. as well."

Fears of an autism epidemic were sparked in 2009 when the Centers for Disease Control and Prevention reported that the rate of autism in children had increased 57 percent since 2002. The most recent data puts the prevalence of autism in children the U.S. at about 1 in 100 -- a similar rate to that found in the U.K. population.

"The CDC studies are showing that the rate of diagnosis has increased," not necessarily the actual number of cases, says Brugha. "What we found is that there is a very low level of recognition of autism in adults, which means that rates may not be increasing, people may just be better at recognizing it."

Autism is still under-recognized in older children, adolescents and adults, says Dr. Nancy Minshew, Director of the NICHD Collaborative Program of Excellence in Autism at the University of Pittsburgh. These older patients "follow a downhill path because the basis of their 'behavior problems' is not correctly understood," she says.

The U.K. findings aren't necessarily surprising to those like Minshew who have studied autism for many years. Because the disorder went largely unpublicized until recently, it is to be expected that there would be a spike in diagnoses once public awareness of autism and other disorders on the autism spectrum increased.

"This is another example where urban myths and urban logic were allowed to dictate public thinking and press coverage, and finally science is bringing up the rear. It takes much longer to demonstrate science than to toss out conjecture," says Minshew.

The study was published in the May issue of Archives of General Psychiatry.

 

ABC NEWS

Related articles

• Autism epidemic? More likely we're just better at diagnosis (arstechnica.com)
• Thousands may have undiagnosed autism (independent.co.uk)
• 'Autism epidemic' dismissed by new claim that thousands of adults go undiagnosed (dailymail.co.uk)
• 6 Common Myths About Autism (everydayhealth.com)

Study of Vision Tackles a Philosophy Riddle

If a blind person were suddenly able to see, would he be able to recognize by sight the shape of an object he previously knew only by touch? Presented with a cube and a globe, could he tell which was which just by looking?

Pause for a moment and think of the answer. Then read on.

The question goes to the heart of a problem in the philosophy of mind: Is there an innate conception of space common to both sight and touch, or do we learn that relationship only through experience? Research published online April 10 in the journal Nature Neuroscience may have finally answered the question, which has vexed philosophers and scientists for more than 300 years.

William Molyneux, an Irish politician and scientist, first raised the issue in a letter to John Locke in 1688. Locke took up what came to be known as Molyneux’s problem in “An Essay Concerning Human Understanding,” published a few years later.

Locke’s answer was no. “He would not be able with certainty to say which was the globe, which the cube, whilst he only saw them,” he wrote, “though he could unerringly name them by his touch.” For Locke, the connection between the senses was learned.

Dozens of philosophers have since considered the problem, among them George Berkeley, Gottfried Leibniz, Voltaire, Diderot, Adam Smith and William James. And some efforts have been made to answer the question experimentally, beginning in the early 18th century with studies of patients whose congenital cataracts had been removed in adulthood and continuing recently in observations of newborns.

But according to the authors of the new experiment, the studies have been inadequate, never establishing how well the patient could see afterward, or failing to test soon enough after surgery so that the subject was still completely inexperienced with vision.

The new research appears to show definitively that Locke was right. The brain cannot immediately make sense of what the eyes are taking in, and the blind man given the ability to see cannot distinguish the two objects. But he can very quickly learn to do so.

Working with a group that provides medical treatment to the blind and visually impaired in resource-poor countries, the researchers tested five subjects from rural northern India, four boys and a girl ages 8 to 17. A all had been blind since birth, one with a disorder of the cornea, and the others with cataracts. Before their operations they could perceive light, and two could discern its direction, but none could see objects. Afterward, they all had vision measured at 20/160 or better, good enough to distinguish objects and carry out the tasks of daily living.

The children were tested within 48 hours of their operations. The researchers placed 20 small objects similar to Lego blocks on a table where they could be seen, but not touched. Then they had the children feel identical blocks under the table where they were invisible, and try to match them with those they could see. The average performance in matching one object with another by either touch or sight alone was high, close to 100 percent. Yet when they were asked to match an object they had felt with an object seen, the average number of correct answers dropped to barely better than chance.

But improvement was rapid. A co-author of the study, Yuri Ostrovsky, a postdoctoral fellow at M.I.T., said one child was proficient in less than a week. Within three months, the average number of right answers in matching an object seen with one touched was above 80 percent.

The senior author, Pawan Sinha, a professor of vision and computational neuroscience at M.I.T., believes that answering the philosophical question is not the only benefit.

“This paper strengthens the case that cross-modal learning is possible despite years of deprivation,” Dr. Sinha said. “That’s very important from a clinical perspective because it argues for making a treatment available to all, irrespective of age. Children beyond 6 or 7 are not beyond the correctable age. The brain retains its plasticity well into late childhood and even into adulthood.”

This article has been revised to reflect the following correction:

Correction: April 28, 2011

An article on Tuesday about a vision experiment that indicated that the neurological connection between sight and touch is learned rather than innate misstated the role of Pawan Sinha of the Massachusetts Institute of Technology. Dr. Sinha was the senior author of a study published in Nature Neuroscience describing the experiment, not the lead author. (Richard Held, also of M.I.T., was the lead author.)

 

NY Times

Related articles

• Formerly Blind Children Shed Light on a Centuries-Old Puzzle (news.sciencemag.org)
• Mapping touch to sight takes time to learn (newscientist.com)
• To touch is to see? (matscience.wordpress.com)
• Mapping touch to sight takes time to learn (newscientist.com)

Study Reveals New Clues to How Depression May Develop

Activating neurons in a brain structure linked to disappointment increased depression-like behaviors in rats, while suppressing the neurons' activity reduced the behaviors, according to an NIMH-funded study. The findings help to explain previous research linking this brain structure to depression in humans and highlight a cellular process that hadn't been previously explored in mood disorders research. The study was published in the February 24, 2011, issue of Nature.

Background

Depression is one of the most studied mental disorders, with research honing in on brain structures, circuits, and biochemical processes critical to the development of the disorder. Yet many questions remain about how changes in the brain result in the observable symptoms and behaviors associated with depression.

To advance the science in this area, Bo Li, Ph.D., of Cold Spring Harbor Laboratory in New York, and colleagues, explored the role and connectivity of neurons in the lateral habenula (LHb) in rats that showed learned helplessness, a set of behaviors similar to symptoms of depression in people. The LHb is associated with how humans and animals experience disappointment or anticipate negative outcomes.

Results of the Study

The researchers found that LHb neurons receive input from many different brain regions involved in responding to stress. LHb neurons also connect out to many brain regions, such as the ventral tegmental area (VTA). The VTA helps to control reward-seeking behavior and may have a role in depression and other mood disorders.

LHb neurons in helpless rats were more responsive, such that communication signals to the VTA were more likely to be transmitted in the helpless rats than in control rats. In an attempt to moderate this phenomenon, the researchers tested the effects of deep brain stimulation (DBS), a surgical procedure currently being tested in humans for treatment-resistant depression. Applying continuous electrical stimulation directly to the LHb resulted in greatly reduced transmission to the VTA and a marked reduction in helpless behavior. The effects on transmission lasted only as long as the stimulation lasted. More intense stimulation resulted in stronger behavioral effects.

Significance

Although LHb activity was previously unstudied in the context of mood disorders, these findings suggest that this brain structure may actually play a central role in the development of depression.

What's Next

Further studies focusing on the molecular processes and signals underlying LHb activity in depression may reveal new targets for treatment development, according to the researchers. Such new treatments also may be able to reverse some forms of depressive disorders.

This study was supported in part by a Biobehavioral Research Award for Innovative New Scientists (BRAINS) from NIMH. Dr. Li was one of 12 researchers to receive this award in 2010.

Lateral habenula neuron labeled with green fluorescent protein. The area marked by a white box is shown at greater magnification in the image on the right.

Source: Bo Li, Ph.D., Cold Spring Harbor Laboratory

 

N IMH

Related articles

• Neuroscientists find overlooked brain area is an important locus of depression (eurekalert.org)
• New Neurons Help Brains Discriminate (technologyreview.in)
• New target structure for antidepressants on the horizon? (eurekalert.org)
• Neurons take naps too (time4sleep.co.uk)

Mayo Clinic Finds Tool to Predict Disability Timeline for Progressive MS Patients

 

Many patients with progressive multiple sclerosis (MS) worry how quickly the disease will progress. Now, by noting the presence of certain markers in a commonly performed diagnostic test, Mayo Clinic researchers can predict whether patients will suffer a faster onset of disability and counsel them to help ease anxiety. The research is being presented at the American Academy of Neurology meeting in Honolulu, Hawaii.

 

Progressive MS is a disease of the central nervous system that can damage the brain, spinal cord and optic nerves. Over time, this damage can make it difficult or impossible for patients to walk, making them reliant on mobility aids such as walkers or wheelchairs.

 

"In this study, we found that in patients who developed the progressive form of MS that had preceding relapses, the presence of greater production of one of these molecules, immunoglobulin G, predicted a faster onset of disability," explains Orhun Kantarci, M.D., a Mayo Clinic neurologist and the study's lead author. As physicians better predict the onset of disability, they can better counsel patients by providing answers in a time of uncertainty.

 

The study looked at cerebrospinal fluid (CSF) test results from a sample of 281 progressive MS patients seen at Mayo Clinic from 2002 to 2007. In general, CSF test results help physicians when the diagnosis is uncertain. For this study, researchers analyzed CSF test results and noticed a relationship between a faster disability rate and abnormally high levels of two proteins — oligoclonal band and immunoglobulin-G molecule. If patients had the progressive form of MS with proceeding relapses, and their CSF results showed an elevated protein, researchers concluded they will have a faster rate of disability.

 

The study is a significant step forward in predicting disability outcomes, says researcher Junger Tang, M.D., a neurology fellow at Mayo Clinic. The next step is further research to confirm the results, he says.

 

MS is the most common cause of nontraumatic neurological disability in young adults in North America and Europe. MS occurs most often in people ages 20 to 40, and is up to three times more common in women than men. Symptoms include weakness, loss of sensation, visual disturbances, and cognitive dysfunction.

 

MayoClinic

Related articles

• Tool predicts disability timeline for progressive multiple sclerosis patients (sciencedaily.com)
• Blocking crucial molecule could help treat multiple sclerosis, Jefferson neuroscientists say (eurekalert.org)
• Mayo Clinic Finds Tool To Predict Disability Timeline For Progressive MS Patients (medicalnewstoday.com)

Federal Researchers Confirms,Armadillos Can Transmit Leprosy to Humans

 

Few armadillos live long enough in the wild to be seriously affected by the infection.

 

Armadillos have never been among the cuddly creatures routinely included in petting zoos, but on Wednesday federal researchers offered a compelling reason to avoid contact with the armored animals altogether: They are a source of leprosy infections in humans.

Using genetic sequencing machines, researchers were able to confirm that about a third of the leprosy cases that arise each year in the United States almost certainly result from contact with infected armadillos. The cases are concentrated in Louisiana and Texas, where some people hunt, skin and eat armadillos.

Leprosy, also known as Hansen’s disease, is an ancient scourge that has largely disappeared, but each year about 150 to 250 people in the United States and 250,000 in the world contract the illness. As long as the disease is identified relatively quickly, treatment with antibiotics — a one- to two-year regimen with three different drugs — offers an effective cure. But every year dozens of people in the United States do not recognize their skin lesions for what they are early enough and suffer lifelong nerve damage as a result.

Part of the problem is that doctors sometimes fail to consider leprosy in patients who have not traveled to parts of the world where the disease is endemic, like India, Brazil, Africa, the Philippines and other islands in the Western Pacific. Two-thirds of leprosy patients in the United States are people who have either lived or worked in such places before coming down with the illness.

But in a given year, about 50 to 80 people who have symptoms consistent with leprosy tell their doctors that they have not traveled to such areas or had any contact with someone with a leprosy infection. And in these patients, doctors may mistakenly dismiss consideration of a leprosy infection.

“These patients have always been a puzzle,” said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases.

Now researchers are hoping that their study leads doctors to ask one more question of patients who have skin lesions that are numb in the center: Any armadillos in your life?

Leprosy now joins a host of other infectious diseases — including flu, H.I.V./AIDS and SARS — that are known to have jumped from animals to humans. Flu is thought to have first crossed to humans from migratory waterfowl several hundred years ago. H.I.V./AIDS first crossed from a chimpanzee about 90 years ago.

Dr. Fauci said that about 70 percent of new emerging infectious diseases were known to have animal origins.

But one of the interesting aspects of leprosy is that transmission seems to have gone in both directions. Leprosy was not present in the New World before Christopher Columbus, and armadillos are indigenous only to the New World.

“So armadillos had to have acquired it from humans sometime in the last 400 to 500 years,” said Dr. Richard W. Truman, a researcher at the National Hansen’s Disease Program in Baton Rouge, La., and an author of the armadillo study, which was published Wednesday in The New England Journal of Medicine.

Some studies have shown that as many as 20 percent of armadillos in some areas are infected with leprosy.

Armadillos now range from Colorado to North Carolina and have a similar habitat to opossums. Few armadillos live long enough in the wild to be seriously affected by the infection, Dr. Truman said, but those in laboratories suffer many of the same problems as humans and eventually die of liver and kidney failure.

The microbe that causes leprosy, Mycobacterium leprae, is a fragile one. It does not grow in laboratory petri dishes, and survives only a week or two in moist soil. Indeed, the only animals in which it is known to flourish are humans and armadillos, and researchers have long used armadillos to grow the disease, although its presence in armadillos predates such research. Because of this, researchers have speculated that some share of human leprosy cases reported in the United States and other parts of the Americas resulted from contact with armadillos, but there has not been definitive proof until this study.

The fragility of the leprosy bacterium suggests that infections result from something more than casual contact with an armadillo, Dr. Truman said.

“The important thing is that people should be discouraged from consuming armadillo flesh or handling it,” Dr. Truman said.

 

 NY Times

Scientists take big steps toward 'bionic' leg

As 20-year-old Hailey Daniswicz flexes muscles in her thigh, electrodes attached to her leg instruct a computer avatar to flex its knee and ankle — parts of Hailey's leg that have been missing since 2005.

Daniswicz, a sophomore at Northwestern University who lost her lower leg to bone cancer, is training the computer to recognize slight movements in her thigh so she can eventually be fitted with a "bionic" leg — a robotic prosthesis she would control with her own nerves and muscles.

"We're really integrating the machine with the person," said Levi Hargrove, a research scientist at the Rehabilitation Institute of Chicago's Center for Bionic Medicine who is leading the project.

Daniswicz is part of a clinical trial sponsored by the U.S. Army that is using electromyography — electrical signals produced by muscles — and pattern recognition computer software to control a new generation of robotic limbs.

Electrodes attached to nine different muscles in the thigh act as antennas, picking up electrical signals sent from the nerves to the muscles. These signals are fired in a specific pattern depending on how a person intends to move.

With a bit of training, the computer can learn a person's signal pattern for when they want to bend a knee or flex an ankle and it makes the virtual reality avatar move.

"The way most prosthetics work now is you have mechanical sensors. You have to push and interact with them," Hargrove said. "With this, you measure the actual neural intent and have that tell the motor what to do."

Researchers at the institute have already developed prosthetic arms directed by nerve impulses. But a robotic leg would give lower limb amputees a new kind of freedom, allowing them to climb stairs more safely and with more natural motion.

Daniswicz has been training her computer avatar since January and she can now instruct it to bend and straighten its knee, and flex and straighten its ankle, just by making slight movements in her thigh muscles.

"Hailey has taught the computer what to do, and now, whenever she does it, it listens, interprets and makes the leg on the virtual reality avatar move," Hargrove said.

Daniswicz is one of four volunteers in the study trial that set out to determine whether patients would need surgery to implant additional nerve endings — a technique called targeted muscle reinnervation — to control the motorized leg.

The team had expected patients to be able to operate the knee joint, but were surprised they could control the ankle without needing surgery, Hargrove and colleagues reported this week in the http://www.msnbc.msn.com/id/42685272/ns/health-health_care/

Since the trial ended, three more volunteers have had similar results.

"The fact that these findings suggest that you might not need surgery makes the population very broad," Hargrove said.

Currently, there are roughly 2 million lower leg amputees in the world, but that figure is expected to double by 2050 as the number of people with diabetes increases, said Michael Goldfarb, a mechanical engineer at Vanderbilt University in Nashville.

Goldfarb's team is developing a fully robotic lower leg for the project that can be controlled by nerve impulses.

He said most lower limb prosthetics are fairly passive.

"They are better than peg legs," Goldfarb said, "but the amputee has to swing it to get the leg to move."

He said advances in robotic technology are making powered legs possible. "It's a much closer approximation to what our own limb does."

Although a few companies are developing powered knees and ankles, no company makes a lower leg prosthetic with both. And none are controlled by the amputee's nerve signals, he said.

For Daniswicz, the next step is a powered leg.

"We'll make a socket for Hailey. We'll put the electrodes in the same location and have Hailey repeat this motion to control a knee and an ankle," Hargrove said.

"After that, we'll start working on transitions from chairs, and then we'll move to walking," he said.

By the end of the year, Hargrove expects to have patients walking in the lab, and then they can try more challenging activities such as stair climbing and descent.

Hargrove said it is too early to say how long it would be before a "bionic leg" would be available.

"It's through research like this that is making it real."

MSNBC

Two mothers confront CP, push for cure

Cynthia Frisina Gray stooped to free her daughter Cathryn’s foot from the Velcro straps of an adaptive bike while Cathryn's big sister, Ally, 12, worked on loosening the other foot.

The Alpharetta mother found nothing similarly collaborative when she learned Cathryn, 10, had cerebral palsy at 11 months old. After a difficult pregnancy and an early delivery, Frisina Gray had a feeling the looseness in her baby’s body wasn’t normal, even though pediatricians assured her it was.

Cerebral palsy is caused by a brain injury that occurs sometime between pregnancy and age 3. The injury creates muscle problems that vary greatly. People with CP can have difficulty walking, talking and caring for themselves. Yet, the condition rarely affects intelligence.

“The neurologist diagnosed her with CP and didn’t give me any information," Frisina Gray said. "I went home and Googled it, and found nothing. The stuff I did find was horrible. There was nothing positive.”

Life changed quickly after the diagnosis. Summertime surgeries replaced family trips. Frisina Gray quit the marketing job she loved -- and the paycheck that was hard to live without -- to take care of Cathryn full time and master new skills required of her, like diaper-changing for incontinence, pain management, choking protocol, obtaining handicapped parking permits and finding the right fit for a school.

“I wanted to find a parent group because there are groups for everything you can think of, but there wasn’t a CP parent group at all," Frisina Gray said.

The family’s confusion only grew as a bevy of doctors were unable to agree on diagnoses, treatments and prognoses for Cathryn. An Atlanta orthopedic specialist eventually introduced Frisina Gray to another mom, Anna Marie Champion, whose daughter Morgan also had CP.

“We clicked right from the start because we’re both parents who were on a mission to find answers to questions that had not been asked,” said Champion of Cumming.

In 2004, the two moms founded Reaching for the Stars: A Foundation of Hope for Children with Cerebral Palsy, a nonprofit that supports federally funded CP research, with the hope of discovering prevention and a cure. RFTS has seven chapters around the country and 10,000 parents in its database. There is no staff and no one gets paid to work for RFTS.

"That's my office right there," said Frisina Gray, pointing to her laptop on an ottoman in her living room. It's the only national parent-run CP nonprofit. The group uses social media, e-mail newsletters and other marketing to draw attention, medical experts and celebrities to conferences and fundraisers. RFTS helped secure the resolutions that led to National Cerebral Palsy Awareness Day, which is March 25.

At a March 3 event at the Center for Disease Control and Prevention, author John Quinn and actor Ashton Kutcher’s twin brother, Michael, spoke about living with CP. Kutcher spent years denying he had the disability that mildly affected his speech and full function of his right hand.

“Society has shunned it so much," Kutcher said. "I was on a mission to live a normal life, so I didn’t want to talk about it. I had yet to accept that I had CP.”

Kutcher changed his mind and agreed to speak at a fundraiser to establish an RFTS chapter in Cedar Rapids, Iowa. Since then, he’s become something of a delegate for the foundation and is working with Frisina Gray on a memoir about his life.

In September, Kutcher, Champion and Frisina Gray lobbied for RFTS in Washington, meeting with Iowa Sen. Chuck Grassley about $10 million in research funds. RFTS's efforts previously had caught the attention of the CDC.

“We got a call at the CDC saying, ‘Do you know who these women are in Washington who are making this case for more research?' We didn't know who they were,” said Dr. Marshalyn Yeargin-Allsop, a medical epidemiologist and chief of the CDC's Developmental Disabilities Branch.

“We were impressed at how they mobilized so many people and were getting CP so much recognition while looking for a cure.”

 

ajc.com

Reaching For The Stars

Related articles

• Some patients with cerebral palsy have asymmetric pelvic bones: Study (news.bioscholar.com)
• Decline in CP diagnoses in premature infants suggests improvements in perinatal care (scienceblog.com)
• Cerebral Palsy Boy Treated With Own Cord Blood Stem Cells (medicalnewstoday.com)

Ecuadorean Villagers May Hold Secret to Longevity

People living in remote villages in Ecuador have a mutation that some biologists say may throw light on human longevity and ways to increase it.

A 67-year-old man who has Laron-type dwarfism with his daughter, 5, and sons, 7 and 10.

 

The villagers are very small, generally less than three and a half feet tall, and have a rare condition known as Laron syndrome or Laron-type dwarfism. They are probably the descendants of conversos, Sephardic Jews from Spain and Portugal who were forced to convert to Christianity in the 1490s but were nonetheless persecuted in the Inquisition. They are also almost completely free of two age-related diseases, cancer and diabetes.

 

A group of 99 villagers with Laron syndrome has been studied for 24 years by Dr. Jaime Guevara-Aguirre, an Ecuadorean physician and diabetes specialist. He discovered them when traveling on horseback to a roadless mountain village. Most such villages are inhabited by Indians, but these were Europeans, with Spanish surnames typical of conversos

.

 

As Dr. Guevara-Aguirre accumulated health data on his patients, he noticed a remarkable pattern: though cancer was frequent among people who did not have the Laron mutation, those who did have it almost never got cancer. And they never developed diabetes, even though many were obese, which often brings on the condition.

A 32-year-old community leader and artist who has the rare dwarfism condition, with his bride, 17.

 

“I discovered the population in 1987,” Dr. Guevara-Aguirre said in an interview from Ecuador. “In 1994, I noticed these patients were not having cancer, compared with their relatives. People told me they are too few people to make any assumption. People said, ‘You have to wait 10 years,’ so I waited. No one believed me until I got to Valter Longo in 2005.”

 

Valter D. Longo, a researcher on aging at the University of Southern California, saw the patients as providing an opportunity to explore in people the genetic mutations that researchers had found could make laboratory animals live much longer than usual.

 

The Laron patients have a mutation in the gene that makes the receptor for growth hormone. The receptor is a protein embedded in the membrane of cells. Its outside region is recognized by growth hormone circulating through the body; the inside region sends signals through the cell when growth hormone triggers the receptor.

 

The Laron patients’ mutation means that their growth hormone receptor lacks the last eight units of its exterior region, so it cannot react to growth hormone. In normal children, growth hormone makes the cells of the liver churn out another hormone, called insulinlike growth factor, or IGF-1, and this hormone makes the children grow. If the Laron patients are given doses of IGF-1 before puberty, they can grow to fairly normal height.

This is where the physiology of the Laron patients links up with the longevity studies that researchers have been pursuing with laboratory animals. IGF-1 is part of an ancient signaling pathway that exists in the laboratory roundworm as well as in people. The gene that makes the receptor for IGF-1 in the roundworm is called DAF-2. And worms in which this gene is knocked out live twice as long as normal.

 

The Laron patients have the equivalent defect — their cells make very little IGF-1, so very little IGF-1 signaling takes place, just as in the DAF-2-ablated worms. So the Laron patients might be expected to live much longer.

 

Because of their striking freedom from cancer and diabetes, they probably could live much longer if they did not have a much higher than usual death rate from causes unrelated to age, like alcoholism and accidents.

 

Dr. Longo said he believed that having very low levels of IGF-1 was the critical feature of the Laron patients’ freedom from age-related diseases. In collaboration with Dr. Guevara-Aguirre, he exposed human cells growing in a laboratory dish to serum from the Laron patients. The cells were then damaged with a chemical that disrupts their DNA. The Laron serum had two significant effects, the two physicians reported on Wednesday in Science Translational Medicine.

 

First, the serum protected the cells from genetic damage. Second, it spurred the cells that were damaged to destroy themselves, a mechanism the body uses to prevent damaged cells from becoming cancerous. Both these effects were reversed when small amounts of IGF-1 were added to the serum.

 

Dr. Longo said that some level of IGF-1 was necessary to protect against heart disease, but that lowering the level might be beneficial. A drug that does this is already on the market for treatment of acromegaly, a thickening of the bones caused by excessive growth hormone. “Our underlying hypothesis is that this drug would prolong life span,” Dr. Longo said. He said he was not taking the drug, called pegvisomant or Somavert, which is very hard to obtain.

 

A strain of mice bred by John Kopchick of Ohio University has a defect in the growth hormone receptor gene, just as do the Laron patients, and lives 40 percent longer than usual.

 

Dr. Longo said that his report had first been submitted to Science, a better-known journal, which turned down the paper because of an adverse report from one reviewer.

 

Andrzej Bartke, a gerontology expert at Southern Illinois University, said that the new result was “very important” and that the authors had done a fine job in following the patients and generating high-quality data. “This fits in with what we are learning from studies in animals about the relationship of growth hormone to aging, because both cancer and diabetes are related to aging,” Dr. Bartke said.

 

The longest-lived mouse on record is one studied by Dr. Bartke. It had a defect in its growth hormone receptor gene, just as do the Laron patients. “It missed its fifth birthday by a week,” he said. The mouse lived twice as long as usual and won Dr. Bartke a prize presented by the Methuselah Foundation (which rewards developments in life-extension therapies) in 2003.

 

Dr. Guevara-Aguirre said he had been struggling to get sufficient IGF-1 to treat 30 of his patients before they reached puberty, at which point it will be too late. He said his group of Laron patients, the largest in the world, had provided essential data for drug companies making IGF-1, and he chided the companies for not reciprocating by providing the drug for his patients.

 

Dr. Arlan Rosenbloom, a pediatric endocrinologist at the University of Florida who has worked with Dr. Guevara-Aguirre, took a similar position. “Considering that the drug companies needed the initial studies to determine dosage and efficacy, it seems ironic that we should have so much difficulty getting the drug,” he said.

 

Ownership of the drug has passed through several companies’ hands, so any initial obligation may have been weakened. Dr. Guevara-Aguirre also said he believed that the government of Ecuador should do more to help get the drug for his patients.

 

Dr. Harry Ostrer, a geneticist at New York University who is exploring the Laron patients’ degree of Sephardic ancestry, said that he had seen several of Dr. Guevara-Aguirre’s patients in Quito, Ecuador’s capital, and that they were “remarkably youthful in appearance.”

 

NY Times

 

Related articles

• Short Ecuadorians hold anti-aging secret (msnbc.msn.com)
• Clues to Fighting Diabetes, Cancer Seen in Short Ecuadoreans (aolhealth.com)
• Short Andeans have a big cancer-fighting secret (newscientist.com)

Molecule switch' protein may point to new treatments for autoimmune diseases

Sientists have found a protein that acts as a “master switch” to determine whether certain white blood cells will boost or dampen inflammation, a finding that may help the search for new drugs for rheumatoid arthritis.

Many patients with rheumatoid arthritis are treated with a class of drugs known as tumour necrosis factor (TNF) inhibitors made by various drug firms including Abbott Laboratories, Merck & Co, Pfizer and Amgen

But around 30% of patients don’t respond to anti-TNF drugs, so experts say there is an urgent need to develop more widely effective treatment options.

In this study, scientists from Imperial College in London found that a protein called IRF5 acts as a molecular switch that controls whether certain white blood cells, known as macrophages, will promote or inhibit inflammation.

In a report of their findings in the journal Nature Immunology on Sunday, they said the results suggest that blocking the production of IRF5 in macrophages might be an effective way of treating a wide range of autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, lupus and multiple sclerosis. They also suggest that boosting IRF5 levels might help treat people whose immune systems are weak, compromised or damaged.

“Our results show that IRF5 is the master switch in a key set of immune cells, which determines the profile of genes that get turned on in those cells,” Irina Udalova, senior researcher on the study, said in a statement.

“This is really exciting because it means that if we can design molecules that interfere with IRF5 function, it could give us new anti-inflammatory treatments for a wide variety of conditions.”

The researchers said IRF5 seems to work by switching on genes that stimulate inflammatory responses and dampening genes that inhibit them. It can do this either by interacting with DNA directly, or by interacting with other proteins that themselves control which genes are switched on, they explained in their study.

Udalova’s team is now studying how IRF5 works at a molecular level and which other proteins it interacts with so that they can design ways to block its effects.

Rheumatoid arthritis is a chronic inflammatory disease affecting around 1% of the world’s population and arises when the immune system mistakenly attacks joints all over the body. As well as joints, it may also affect the skin, heart, lungs, kidneys and blood vessels. Many sufferers get deformed hands and feet, which hamper movement and ability to function.

 

National Post

Related articles

• Scientists find inflammation immune cell switch (reuters.com)
• Scientists find the 'master switch' for key immune cells in inflammatory diseases (eurekalert.org)
• Scientists find the 'master switch' for key immune cells in inflammatory diseases (scienceblog.com)

New Brain Tumor Vaccine To Be Tested In Humans

For patients with low-grade gliomas, or slow growing brain tumors, a shot in the arm might soon lead to a new treatment therapy. A groundbreaking, first in humans vaccine will be tested in an early phase clinical trial that will soon begin at Wake Forest University Baptist Medical Center. Eighteen patients will be the first in the world to receive it.

“This study is looking at a very new form of treatment called a preventative brain tumor vaccine. The idea is to treat the low-grade glioma and to prevent it from growing back,” said Edward Shaw, M.D., a radiation oncologist. “In this early phase study, we are looking to see whether the patient develops an immune response against this kind of brain tumor, a necessary step for the vaccine to work.”

The trial is a bi-institutional pilot study, funded by the National Cancer Institute, and shared with the University of Pittsburgh (UP). Wake Forest Baptist and UP will enroll nine patients each.

The vaccine will be administered to adult patients who have been diagnosed and had surgery for the removal of a low-grade brain tumor. They will receive the vaccine every three weeks for six months. A simple blood test will determine whether an immune response has developed.

Brain tumors are relatively uncommon when compared to other types of cancer, Shaw points out, but they are the most common cause of cancer death in children.

Low-grade gliomas are the most common primary brain tumors and usually affect children and young adults in their 20s, 30s and 40s. Low-grade gliomas often recur after surgery and radiation and may progress to a higher grade, more aggressive brain tumor. When they do, there is no curative treatment.

“If we can prevent the tumor from growing back or from transforming to a more malignant form, the hope is that we can cure more low-grade glioma patients,” Shaw said.

The vaccine is the culmination of years of research and an interesting partnership that brings together three great scientific minds and their individual areas of expertise. Wake Forest Baptist has long been a leader, nationally and internationally, in the diagnosis and treatment of low-grade gliomas, and Shaw has led many of the research studies involving this type of tumor for the last 25 years.

Shaw teamed up with Waldemar Debinski, Ph.D., director of the Brain Tumor Center of Excellence at Wake Forest Baptist, who discovered several of the glioma-associated antigens or molecules recognized by the immune system as foreign and targeted by the vaccine.

The vaccine was developed by UP’s Hideho Okada, M.D., Ph.D., the third side of this scientific triangle, and is based in part on Debinski’s discoveries.

BioMedMe

Do Kids of Divorce Have Strokes More Often?

 

Of all the odd and unexpected consequences of divorce — missing kitchen utensils, kids with two sets of everything, a weird sense of sadness yet liberation — this is a new one. A cross-sectional study of 13,000 Canadians found that people whose parents had divorced had significantly higher risk of stroke in later life, compared with those whose parents stayed married.

The study, conducted by University of Toronto professor Esme Fuller Thompson and graduate students Angela Dalton and Rukshan Mehta doesn't prove that a couple's divorce will cause strokes in their kids. But it does find an intriguing association: the children of parents who split had twice the odds of stroke of people of the same age who grew up in a family that remained together

The researchers, who presented their findings at The Gerontological Society of America's annual meeting in New Orleans on Nov. 22, controlled for education, income, race, sex, diabetes and other variables. Even when adjusted for all that, the association remained. "The link does not appear to be due to adult health behaviors, adult socioeconomic status, mental health or diabetes," says Fuller Thompson.

As far as the researchers are aware this is the first study that has come upon this connection and Fuller Thompson cautions that the results need to be replicated by somebody else. "There are several potential mediators we could not investigate in this study," she says, including diet, cholesterol levels, blood pressure, family history of stroke, childhood socioeconomic status.

That last one may be a doozy, since divorces, especially those of, say, 50 years ago (when the stroke sufferers in the study would have been children), were probably rarer, more stressful and more likely to impoverish their mothers, who were less likely than modern women to have been employed outside the home.

But that's just a hypothesis. "Research on childhood poverty and on childhood abuse suggests that severe and chronic stress in childhood can adversely impact the way that child will physiologically respond to the stressors they face across the whole life course," says Thompson Fuller. "Hopefully future research could shed some light on what role, if any, cortisol [the fight or flight hormone we produce when stressed] plays in the parental divorce-stroke association."

Fuller Thompson next wants to analyze other large representative community studies to see if the link crops up in those as well. And she hopes others will do similar studies on other health issues. "Hopefully this study will inspire other researchers to consider whether parental divorce is associated with other physical health outcomes."

TIME.COM

First patient treated in embryonic stem cell trial

 Controversial cells being used to help patient with spinal cord injuries

 

U.S. doctors have begun treating the first patient to receive human embryonic stem cells, but details of the landmark clinical trial are being kept confidential, Geron Corp said on Monday.

Geron has the first U.S. Food and Drug Administration license to use the controversial cells to treat people, in this case patients with new spinal cord injuries. It is the first publicly known use of human embryonic stem cells in people.

"The patient was enrolled at Shepherd Center, a 132-bed spinal cord and brain injury rehabilitation hospital and clinical research center in Atlanta, Georgia," Geron said in a statement.

"Shepherd Center is one of seven potential sites in the United States that may enroll patients in the clinical trial."

Northwestern University in Chicago is also ready to enroll patients.

Geron's stem cells come from human embryos left over from fertility treatments. They have been manipulated so that they have become precursors to certain types of nerve cells.

The hope is that they will travel to the site of a recent spinal cord injury and release compounds that will help the damaged nerves in the cord regenerate.

The Phase I trial will not be aiming to cure patients but to establish that the cells are safe to use. Under the guidelines of the trial, the patients must have very recent injuries.

Geron said the Shepherd Center would keep details of the patient confidential."When we started working with human embryonic stem cells in 1999, many predicted that it would be a number of decades before a cell therapy would be approved for human clinical trials," Geron President and CEO Dr. Thomas Okarma said in a statement.

Geron is not subject to limitations on federal funding for human embryonic stem cell  research, as it has done all its work with its own funding.

The government is embroiled in a legal battle over the cells. Just weeks after he took office in 2009, President Barack Obama issued an executive order that eased limitations on federal funding of human embryonic stem cell research.

Opponents of their use say it is wrong to use a human embryo to make the cells, and two researchers have sued the National Institutes of Health . A federal appeals court has allowed continued federal funding of the work until the case is heard.

Stem cells are the master cells of the body, giving rise to blood cells and tissue. Those taken from days-old embryos are the most powerful of all, giving rise to every tissue and cell type.

While scientists have hoped that stem cells could transform medicine, providing cures for diseases such as Parkinson's and juvenile diabetes. the reality has been that they are difficult to work with and do not easily grow into new tissues.

Besides Geron, only one other company -- Massachusetts-based Advanced Cell Technology -- has a human embryonic stem cell treatment close to FDA approval.

ACT's product is a human embryonic stem cell trained to become a retinal cell. The company has asked the FDA for permission to use it in patients with Stargardt's macular dystrophy, a genetic eye disease that progresses to blindness.

 

MSNBC

In death, a promise for the future

All of  the stories i post i feel are all amazing and some very powerful personal  stories. This one made me laugh & cry. I could feel the hurt & frustration Elizabeth Uyehara felt.Maybe the fact her story is being  told to us I try to imagine how it may sound from her and those close to her.

Elizabeth Uyehara met her husband, Paul, at Otis College of Art and Design in Los Angeles. They exhibited together at local galleries. (Bob Chamberlin / Los Angeles Times / April 6, 2010)

If Elizabeth Uyehara were alive, she would be pleased. Everything was working out as she had hoped. The terrible banality of her illness had ended, and she was about to make her final journey.

Two hours before she died, David Jones' pager went off. He canceled his lunch and made a few phone calls to sort out the details with the hospital and the family. He went to his lab and picked up the paperwork and, before heading over the Sepulveda Pass, stopped at a 7-Eleven for some ice that he tossed into a cooler.

He parked in the back of the mortuary in Northridge and let himself into the prep room. Her body lay on the porcelain table. He walked over to the cabinet where he kept his instruments, pulled on two pairs of size-81/2 surgical glovesHe still remembers seeing her there. She was 75 years old, 5 feet 5, a little less than 111 pounds, brown hair, brown eyes. He read her toe tag and wrist bracelet and double-checked her name and date of birth.

Schooled in mortuary science, Jones had been performing autopsies and harvesting organs for 30 years; by his count more than 11,000 bodies. Whether by habit or instinct — he wasn't sure — he always paused at this moment.

Here was someone's loved one, he thought; you were brought to me for a reason: that someday we might help someone else.

Uyehara would have returned the sentiment.


She had always been sensitive about her health. Nothing was too extreme to worry about, so four years ago, when she found herself slurring her words and her vision suddenly blurry, she made an appointment with a neurologist.

It could be a number of things, he suggested: cancer, stroke, progressive bulbar palsy, neuromuscular dystrophy, even Lou Gehrig's disease. She listened, dumbstruck. He's measuring me for a coffin, she thought, and she went looking for a second, then a third opinion.

She was tested and re-diagnosed. She was told she had Stephen Hawking's disease. She was told she had Dudley Moore's disease. One doctor admitted he didn't know what she had. At least he was honest, she thought.

Nearly a year and a half went by. Someone had mentioned myasthenia gravis. Its description — slurred speech, blurred vision, fatigue — matched her symptoms. She felt encouraged; typically it wasn't fatal. She made an appointment for another test.

This time a needle electrode was inserted an inch into her muscles, and as she tensed and relaxed, a machine recorded the activity. When it was over, the news wasn't good.

A relaxed muscle results in a reading close to zero and is almost silent; in her case, the reading was 3-plus and accompanied by a cacophonous and irregular sound, an indication that the nerves leading to the muscles were beginning to fail. When she flexed, the results were more dramatic

She found herself in the company of yet another celebrity.

"Lou Gehrig's disease," she heard the neurologist say. Amyotrophic lateral sclerosis, ALS.

She started to cry. It would take a few weeks to find a comeback:

"Does this mean I can finally hit a major league fastball?"

Beneath the fluorescent lights in the windowless room, Jones pulled on shoe covers, a gown and a face shield and laid out his instruments. He cued his CD player to the gospel strains of the Edwin Hawkins Singers and placed a small rubber block beneath her head. If he felt any emotions, he kept them in check.

With a Stryker saw, he cut a circle around her cranium and removed the cap. He used a syringe to extract the spinal fluid between the hemispheres, and afterward he cradled her head with one hand, reached around the brain and with a scalpel freed it from the stem. He lifted out both hemispheres and placed them in a plastic bag and put the bag on ice.

He opened her chest with a deep Y-shaped incision and sawed through her ribs. He withdrew about 60 milliliters of blood from the inferior vena cava and then removed her heart. He excised her liver, spleen, pancreas, lungs, kidneys, adrenal and thyroid glands, uterus, bladder and large and small bowels and cut samples from each.

The spine was now exposed, and he sawed through the vertebrae and freed the cord, a half-inch-diameter bundle of nerves, roughly 2 feet long, soft and white. He coiled it into a round plastic container.

By late afternoon, he began positioning the organs back inside her, and with nylon thread and a baseball stitch, he sewed her up. He didn't know whether she would be cremated or whether there would be a viewing, but that didn't matter. He always made sure his work was as inconspicuous as possible.

With water, soap and a soft towel, he washed her off and pulled the body bag around her.

She feared ALS but never considered it a possibility. It wasn't her style, so dramatic: no treatment, no remission, just muscles shutting down to the point of suffocation.

She was certain her death would be less flashy — a heart attack or a pile-up on the freeway — and until then, she'd live at home in Reseda, painting and taking care of her cats and husband, Paul. He was nine years older and showing signs of Parkinson's. They never had children and managed on their Social Security and a pension from her years working in the marketing department at the Los Angeles Times.

But when she Googled "ALS bulbar onset," she learned that patients with her form of the disease typically live 18 months after the first symptoms emerge. She did the math. Her expiration date had come and gone, she thought, which could mean only one thing:

She was never going to know how "Lost" ended.

She started seeing a doctor at UCLA, Martina Wiedau-Pazos, and arrived to each appointment with typed notes and questions.

ALS was unlike anything she had experienced. The more moderate symptoms and sensations — the yawning, sneezing, hiccupping — she could handle, but the involuntary fits of laughing and crying were a bit much. Tears were hard to explain to the clerk who simply wanted to know "Paper or plastic?"

One day she put a key in a lock and couldn't understand why it didn't turn. She pulled it out. It was the right key, wasn't it? She tried again. The lock had to be broken. Then it dawned on her: She had lost the strength in her fingers.

The disease became a hundred little battles waged in a losing war. She taught herself a new way to use a paper clip and light a match, and with the help of a speaking device attached to her computer, she could type and it would talk.

Eating was her first major defeat. As her tongue stopped working, she changed her diet to smoothies and oatmeal. Still she choked, and her doctor worried she might aspirate. A feeding tube was prescribed.

She missed her salads but made do, injecting a regular diet of Ensure and protein supplements into her stomach. Life, she explained to a friend, does not have to be lived in the extreme. "You can be fully alive by just being alive in your body."

Chocolate was a clear victory. If she tucked a Hershey's Kiss into her right cheek, lay down on her side and let it melt, she could still savor its sweetness.

Saturday evening traffic was light as Jones drove into West L.A. He had skipped lunch and now he'd miss dinner, but he needed to finish.

The National Neurologic AIDS Bank is a UCLA facility that archives brain and spinal tissue for researchers studying AIDS-related neurological disorders. Although the bank is funded for the study of AIDS, its collection has come to include tissue from HIV-negative patients and individuals with ALS and brain cancer.

Jones unlocked the door to the lab. He laid the heart and the smaller tissues on the counter and cut them in two, and divided the brain by its hemispheres. He sectioned the spine into thirds — thoracic, lumbar and cervical — and sliced each length into 1-centimeter increments. Half the samples went into formalin preservative, the other half into the freezer. Its frosty air purled into the room as Jones opened the door.

He glanced at the clock, a little past midnight. He went to his computer and sent an e-mail to the lab's staff. Elizabeth Uyehara, he typed, "passed away on 3/6/2010 at 2:27 p.m. The brain was on ice at 6:30 p.m."


A friend suggested that she start a blog, but she was reluctant. Jeering at ALS was fine if done in private, but she worried that her irreverence might offend those further along with the disease.

Still she knew the value of words, and on June 23, 2008, posted her first entry. "I might as well join the rest of the human race," she wrote, "and start blogging to kill a little time, since time is busily returning the favor."

She also made friends on an ALS forum, venting frustrations, discussing medications and cracking jokes

"Q: When you're lying in your casket, what do you most want your friends to say?

A: Look, he's moving".

There were times when she felt suicidal. But they passed, and what remained was a cobbled-together spiritualism based on the 12-step program, the Upanishads, Buddhism, yoga, Pink Floyd, Leonard Cohen and Freud. It was enough to sustain her.

"We are not really humans looking for spiritual experiences," she paraphrased a mentor. "We are spiritual beings looking for human experiences."

Now if only those experiences had less to do with trying to find a skilled nursing facility for herself and Paul, paying income taxes and fighting her insurance company for a power wheelchair.

After she had decided to give her body to UCLA, she tacked on one provision in a blog post: that the university, once done "ooo-ing and ahh-ing" over her spine, "donate it to the Democratic Party."


Wiedau-Pazos sees patients for only a few hours each week. Most of her time is spent in her office or the lab on the fourth floor of UCLA's Neuroscience Research Building, where she has been studying ALS since 1995.

About 35,000 people in the country have the disease. Some cases are hereditary; most are sporadic. In each, motor neurons — long thin fibers that run from the brain through the spine to the muscles — degenerate, leaving the muscles to atrophy and the patient paralyzed.

No one knows why. Wiedau-Pazos is studying the possibility that ALS is a disease of the immune system, like multiple sclerosis and lupus. She and other researchers have uncovered evidence — an elevated number of white blood cells in the spinal cords of ALS patients — but they are uncertain whether the proliferation of these cells causes ALS or is the result of ALS.

This spring the doctor began a new round of studies and needed samples from five brains and spinal cords.

ALS was writing the final chapter to her life. What had once seemed so important — her ambition as a painter, her identity as a wife, an aunt, a cousin and a friend — mattered less as she grew weaker.

"We sit in empty rooms," she wrote her cousin one rainy afternoon in January, "but between us and the walls, there is endless chemical and electrical activity, molecules [and] the air is filled with star dust…. There is no emptiness, only endless pulsing energy."

Perhaps in death, released from her body, she would join that energy. She began to look forward to dying. She found a Vedic prayer to be spoken at the end: "… let my life now merge with the all-pervading life … ashes are my body's end." But it was too long to memorize.

She wondered instead if her final words would be more like aaaaaeeeeeiiiiiii.

If she did utter a prayer or scream one morning last March, no one heard. She was having difficulty breathing and arrived unconscious at the emergency room. The doctors had intubated her by the time two friends and her niece arrived. The niece went home to get Paul. He shuffled up to her hospital bed.

"I love you," he said.

There was little else to be done, and he was taken home.

After the breathing tube was removed, the niece held her aunt's hand and watched and listened as the heart rate slowed.

"Keep a place in line for me," her niece said, and the room grew silent.


Wiedau-Pazos opened up the green slide carrier and pulled out eight slides. Each contained a nickel-size cross-section of the cervical spinal cord, sliced by a microtome, as fine as an eyelash, preserved and embedded in paraffin.

She held up No. 3038 and kept her memories in check. In the lab, there was no past, no personal history, just the present moment and what it might reveal.

After the tissue was properly stained, Wiedau-Pazos placed the slide under the microscope and peered through the eyepiece. The anterior horn of the spinal cord was brilliantly colored. The sliver of tissue looked like the night sky seen through a red filter. The motor neurons were the stars, and a cluster arcing through it, the Milky Way.

Elizabeth Uyehara was now a portrait of proteins, sugars, phosphates and amino acids, and they belonged to the future, a story waiting to be told.

LA TIMES

ALSorg

Related articles by Zemanta

• You: In death, a promise for the future (latimes.com)
• Was Lou Gehrig Misdiagnosed With Lou Gehrig's Disease? (insidesurgery.com)
• Lou Gehrig May Not Have Had Lou Gehrig's Disease (patspapers.com)

Stem-Cell Ruling Gloom and Confusion

Embryonic stem cells, seen through a microscope

Stem-cell scientists still reeling from a judge's ruling that their life's work violates federal law received little reassurance about their job security from the nation's largest funder of these studies, the National Institutes of Health (NIH). Describing stem-cell research as one of the more promising engines of scientific discovery, NIH director Francis Collins said the legal decision "poured sand into that engine of discovery."

Late on Tuesday, a day after U.S. District Judge Royce Lamberth filed his ruling that the NIH's use of taxpayer dollars to fund experiments on human embryonic stem cells violates a 1996 law that prohibits the government from supporting any research that harms or destroys human embryos, the Obama Administration announced that it plans to appeal the judge's preliminary injunction on all such government-funded studies currently under way in the U.S. Left unchallenged for the moment is the ban on pending studies — and there are a lot of them. According to Collins, about 50 new grant applications that were awaiting review by NIH experts were pulled from the agency's evaluation queue and put aside. A planned September meeting of an NIH advisory council to consider an additional dozen grants worth $15-$20 million that have already passed a first-level review and would undergo a second evaluation was canceled, Collins said, because "the council is not even allowed to discuss them." Another 22 grants totaling $54 million are up for an annual review and refunding in September as well, he said, but with Lamberth's decision, "those projects would basically stop in their tracks."

(See the top 10 scientific discoveries of 2009.)

The only good news came for those scientists who, through serendipity, already reupped their annual grant and received their portion of the $131 million that the NIH has issued to scientists this year. Those experiments, said Collins, could continue — at least until they are due for renewal again next year. For the others in the stem-cell community, the ruling represents the worst possible scenario, with the federal government essentially walking away from an entire field of scientific study. "This is clearly sad news for all of us in the U.S. who work with embryonic stem cells," says Kevin Eggan, a principal investigator at the Harvard Stem Cell Institute.

While the appeals process unfolds, stem-cell scientists who had been receiving federal funds and were expecting more will not necessarily have to quit working, but they will have to begin a frenzied money chase, looking for private investors to pick up the bill when their current allocation runs out. That, said Collins, is not going to easy. "It's not clear that private sources would appear to meet that need," he said. "There is considerable jeopardy that a project in the middle of a multiyear effort would be prematurely stopped and the results of that research would be lost."

(See how to prevent illness at any age.)

The success of the Obama Administration's appeal of the new ruling will depend on the higher court's interpretation of when a preliminary injunction — like the one Lamberth issued — is justified. Generally, explains Russell Korobkin, a law professor at the University of California, Los Angeles, and an expert on stem-cell law, a preliminary injunction is issued in cases in which the judge feels a plaintiff is threatened by irreparable harm if the current situation continues without any legal intervention. In this case, the plaintiffs are two scientists who work with adult stem cells, the less versatile cousins of embryonic stem cells. The scientists argued that President Obama's 2009 Executive Order expanding federal funding of studies on the embryonic cells did them harm by making it more challenging for them to compete for government grants to support their work. Korobkin is not sure that the argument will stand. "It is true that there is small reduction in the chance of getting funding if you compete in a bigger pool of applicants," he says, "but to say that the reduction in the chances of getting a grant is irreparable harm, I think, is incorrect. Also, the idea of irreparable harm means the potential harms to both sides are supposed to be compared. How much harm will the government suffer if it was prevented from carrying out its policies? What about the people who now have a reduced chance of a cure for their disease that might have come from embryonic-stem-cell research?"

(See TIME's stem-cell covers.)

Arguing that Lamberth's issuance of a preliminary injunction was not justified may convince an appeals court to prevent the temporary injunction from becoming a permanent one. But if it doesn't, says Korobkin, the government would have to take its case to the Court of Appeals, where it can argue the merits of Lamberth's interpretation of the Dickey-Wicker Amendment, the 1996 law that prohibits federal support of research that harms embryos. The Department of Justice may argue that the language of Dickey-Wicker is clear in prohibiting only research involving the act of destroying embryos and not, as Lamberth maintained, studies of the products of embryos, like embryonic stem cells. The government may rely on precedent as well: in 1999, in anticipation of just such an interpretation of Dickey-Wicker, Harriet Rabb, then counsel for the Department of Health and Human Services, declared that embryonic stem cells were not embryos as defined by Dickey-Wicker and therefore were exempt from the prohibitions of that law. Even the Bush Administration accepted Rabb's decision as a settled interpretation of the law, and in 2001, President George W. Bush allowed federal funds to be used for studying a limited number of embryonic-stem-cell lines already in existence, while preventing taxpayer dollars from generating new stem-cell lines that would require the destruction of embryos.

(See "The Year in Health 2009: From A to Z.")

If this precedent isn't sufficient, says Korobkin, the government still has a backup strategy. "The way the law works in this case is that if a statute is ambiguous, the court is supposed to defer to the interpretation of the administrative agency. In this case, that's the NIH." And the NIH's interpretation of Dickey-Wicker is represented by the Rabb decision — that embryonic stem cells are not embryos and therefore the cells are eligible for federal funding.

Pursuing such a legal strategy could be notoriously frustrating and protracted. In the meantime, warned Collins, leading stem-cell scientists could decamp for more favorable political and legislative environments overseas, or turn their talents to other scientific fields. That would argue for a legislative strategy. Congress could decide to clarify the role of the federal government in embryonic-stem-cell research by passing a law that allows for government support of the field, essentially putting into law what Obama's Executive Order did in 2009. Passing such a law, says Korobkin, would "moot the whole legal case and moot the court proceedings. Congress could step in and say, Here is what we want: we want the government to be able to fund research on embryonic stem cells so long as the government is not directly funding the actual destruction of embryos themselves." In fact, over the past decade, Congress has passed such legislation twice. And twice, Bush vetoed the bill. Obama would surely sign the law if it reached his desk, but the question this time is whether a toxically partisan House and a largely dysfunctional Senate could pull themselves together to pass it. Don't expect an end to the stem-cell roller coaster anytime soon.

See TIME's special report "How to Live 100 Years."

See TIME's health and medicine covers.

TIME

 

Related articles by Zemanta

• Gloom and Confusion in the Stem-Cell Community (time.com)
• Stem-Cell Ruling Causes Gloom, Anxiety Among Scientists (time.com)
• Gloom and Confusion in the Stem Cell Community (time.com)
• Irreparable Harm?: Embryonic Stem Cell Research Blocked (abcnews.go.com)
• "Stem Cell Tragedy: ADF Lawsuit Blocks Badly Needed Medical Research" and related posts (au.org)
• Court rules against Obama's stem cell policy (reuters.com)

Stem Cell Trial Wins Approval of F.D.A.

The world’s first authorized test in people of a therapy derived from human embryonic stem cells has been cleared by the Food and Drug Administration.

The clinical trial could offer the first glimpse of the safety and possible effectiveness of a technology that has been hailed for its vast medical promise but also embroiled in political and ethical controversy.

The trial will test cells developed by the Geron Corporation and the University of California, Irvine in patients with new spinal cord injuries.

The F.D.A. had initially cleared the clinical trial in January 2009. But before any patients could be treated, the agency suspended the trial after cysts were discovered in some rats injected with the cells. Geron had to do another rat study and develop better ways to check cell purity.

On Friday, the company announced that the F.D.A. had lifted the hold. Geron’s shares rose 17 percent, to $5.63.

Embryonic stem cells can turn into any type of cell in the body. Scientists envision one day making replacements for injured or diseased tissues to treat a wide variety of illnesses.

“I think it’s a very important milestone for the whole industry,” Alan Trounson, the president of California’s stem cell agency, said Friday, adding that the hold on the trial had been a cloud over the field. “It’s very important that they get on and treat the patients and demonstrate the safety” of the therapy.

But the cells have been controversial because their creation has involved the destruction of human embryos, though some researchers claim they can now avoid that.

The politics of embryonic stem cell research has shifted from one presidential administration to another, set in sharp relief by religious conservatives who opposed destroying or using human embryos.

President George W. Bush limited federal funding for research to certain colonies, or existing lines of cells. President Obama lifted those restrictions and is gradually approving more lines to qualify for federal funding.

Geron, based in Menlo Park, Calif., turns embryonic stem cells into precursors of neural support cells called oligodendrocytes. The precursor cells would be injected into the spinal cord at the site of the injury.

The hope is that the cells will repair the insulation, known as myelin, around nerve cells, restoring the ability of some nerves to carry signals.

While this is not expected to allow people to rise from their wheelchairs, it may conceivably restore some movement or sensation.

The first trial, a so-called Phase 1 study, will have up to 10 patients and is mainly aimed at testing the safety of the therapy. Years of further testing will be required before the therapy would be proven and ready for widespread use, assuming it works.

Dr. Thomas B. Okarma, the chief executive of Geron, said that the ethical review boards at two of the seven proposed trial sites had already approved the trial, so that it was possible the first patient might be treated in the next few months.

Dr. Okarma would not identify the trial sites, saying the privacy of the patients must be protected from what could be intense interest from the media.

“We can’t let that happen to disrupt the integrity of the trial,” he said in an interview. “The bright lights are going to be on this.”

That concerns some experts, who say that Geron’s therapy does not have that good a chance of working and that a failure or a safety problem could set back the whole field. The biggest safety concern is that if there are any embryonic stem cells left in the mixture that is injected into patients, they could possibly form tumors.

Dr. Okarma said critics had not seen the 28,000 pages of data that Geron had submitted to the F.D.A. “The degree of heavy lifting and turning over every possible stone is not appreciated,” he said.

Patients in the initial trial will have a so-called complete injury, with virtually no chance of spontaneous recovery, Dr. Okarma said. That way, if there is any improvement in their movement or sensation it could be attributed to the treatment.

Another company, Advanced Cell Technology, is trying to win approval from the F.D.A. to test retinal cells derived from human embryonic stem cells as a treatment for Stargardt disease, an eye condition that causes severe vision loss.

In the last few years scientists have become excited about so-called induced pluripotent stem cells as an alternative to embryonic stem cells.

Those cells can be made from an adult skin or blood cells, doing away with the need for human embryos. And if a patient’s own cell could be turned into new tissue it would eliminate the chance the transplanted cells would be rejected by the patient’s immune system. (Geron’s trial will involve temporary use of an immune-suppressing drug.)

Still, some recent laboratory studies have suggested that the induced pluripotent cells might not be quite as versatile as the embryonic cells in turning into different types of tissues.

 

New York Times

Frozen Blood a Source of Stem Cells, Study Finds

Frozen blood from stored samples can be used to make cells resembling stem cells, researchers said on Thursday -- opening a potential new and easier source for the valued cells.

They used cells from blood to make induced pluripotent stem cells or iPS cells -- lab-made cells that closely resemble human embryonic stem cells but are made from ordinary tissue. These iPS cells have in the past been made from plugs of skin, but blood is much easier to take from people and to store, the researchers reported in the journal Cell Stem Cell.

"Blood is the easiest, most accessible source of cells, because you'd rather have 20 milliliters of blood drawn than have a punch biopsy taken to get skin cells," Judith Staerk of the Whitehead Institute for Biomedical Research in Massachusetts, who worked on the study, said in a statement.

Stem cells are the body's master cells, the source of renewed blood and tissue. So-called adult stem cells exist through life but they are partially developed.

Embryonic stem cells from days-old embryos have the ability to become all the cell types in the body and also can proliferate in the lab for years.

IPS cells are made by activating three or four genes that distinguish embryonic stem cells.

Whitehead's Rudolf Jaenisch, who directed the work, said being able to use blood will open opportunities for researchers who want to use iPS cells to study how diseases develop.

"There are enormous resources -- blood banks with samples from patients that may hold the only viable cells from patients who may not be alive any more, or from the early stage of their diseases," Jaenisch said.

"Using this method, we can now resurrect those cells as induced pluripotent stem cells. If the patient had a neuro-degenerative disease, you can use the iPS cells to study that disease."

ABC NEWS

Related articles by Zemanta

• Stem Cells From Human Blood Can Be Reprogrammed (wired.com)
• Stem cells from blood a 'huge' milestone (sciencenews.org)
• Stem Cells From Blood a 'Huge' Milestone (usnews.com)
• Frozen blood a source of stem cells, study finds (reuters.com)