Monday, September 21, 2009

Scientists Make Paralyzed Rats Walk Again After Spinal Cord Injury

UCLA researchers have discovered that a combination of drugs, electrical stimulation and regular exercise can enable paralyzed rats to walk and even run again while supporting their full weight on a treadmill.

Published Nov. 20 in the online edition of Nature Neuroscience, the findings suggest that the regeneration of severed nerve fibers is not required for paraplegic rats to learn to walk again. The finding may hold implications for human rehabilitation after spinal cord injuries.

"The spinal cord contains nerve circuits that can generate rhythmic activity without input from the brain to drive the hind leg muscles in a way that resembles walking called 'stepping,'" explained principal investigator Reggie Edgerton, a professor of neurobiology and physiological sciences at the David Geffen School of Medicine at UCLA.

"Previous studies have tried to tap into this circuitry to help victims of spinal cord injury," he added. "While other researchers have elicited similar leg movements in people with complete spinal injuries, they have not achieved full weight-bearing and sustained stepping as we have in our study."

Edgerton's team tested rats with complete spinal injuries that left no voluntary movement in their hind legs. After setting the paralyzed rats on a moving treadmill belt, the scientists administered drugs that act on the neurotransmitter serotonin and applied low levels of electrical currents to the spinal cord below the point of injury.

The combination of stimulation and sensation derived from the rats' limbs moving on a treadmill belt triggered the spinal rhythm-generating circuitry and prompted walking motion in the rats' paralyzed hind legs.

Daily treadmill training over several weeks eventually enabled the rats to regain full weight-bearing walking, including backwards, sideways and at running speed. However, the injury still interrupted the brain's connection to the spinal cord-based rhythmic walking circuitry, leaving the rats unable to walk of their own accord.

Neuro-prosthetic devices may bridge human spinal cord injuries to some extent, however, so activating the spinal cord rhythmic circuitry as the UCLA team did may help in rehabilitation after spinal cord injuries.

The study was funded by the Christopher and Dana Reeve Foundation, Craig Nielsen Foundation, National Institute of Neurological Disorders and Stroke, U.S. Civilian Research and Development Foundation, International Paraplegic Foundation, Swiss National Science Foundation and the Russian Foundation for Basic Research Grants.

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Tuesday, July 28, 2009

Stem-Cell Breakthrough

It's a chilling thought. In the coming year, 130,000 people worldwide will suffer spinal-cord injuries?in a car crash, perhaps, or a fall. More than 90 percent of them will endure at least partial paralysis. There is no cure. But after a decade of hype and controversy over research on embryonic stem cells?cells that could, among other things, potentially repair injured spinal cords?the world's first clinical trial is about to begin. As early as this month, the first of 10 newly injured Americans, paralyzed from the waist down, will become participants in a study to assess the safety of a conservative, low-dose treatment. If all goes well, researchers will have taken a promising step toward a goal that once would have been considered a miracle?to help the lame walk.

The trial signals a new energy permeating the field of stem-cell research. More than 3,000 scientists recently met in Barcelona for the annual conference of the International Society for Stem Cell Research, compared with just 600 researchers five years ago. Money from major pharmaceutical companies is following the advances. Former U.S. vice president Al Gore, now a partner in the venture-capital firm Kleiner Perkins Caufield & Byers, has thrown his weight behind the research. In April, the firm joined with Highland Capital Partners to invest $20 million in iZumi Bio (now iPierian), a startup firm working on stem-cell therapies.
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Despite the considerable hype surrounding stem cells in recent years, the possibilities now appear to be broader than most people realize. In addition to helping replace damaged cells in patients with diseases like diabetes or Parkinson's, stem cells have the potential to change how we develop drugs and unravel the biology of disease. They may even be used one day to create replacement organs. "There's been a massive injection of optimism into the field," says stem-cell biologist Alan Trounson, president of the California Institute for Regenerative Medicine. "It's remarkable how fast it's progressing."

Much of the excitement comes from the development of a new type of stem cells, called "induced pluripotent" stem cells, or iPS. Shinya Yamanaka first concocted the cells in his Kyoto University lab by inserting four genes into fully formed adult skin cells. They began to behave like embryonic stem cells, capable of forming unlimited copies of any of the body's 220 cell types. Because iPS cells can be derived from a patient's own adult cells, they do not carry the risk of rejection by the immune system. Equally important, because iPS cells are not derived from embryos, they skirt a major ethical and religious problem.

The first iPS cells, however, will not be used as replacement tissue for spinal cords and other organs. Because iPS cells have subtle (and potentially dangerous) differences from true embryonic stem cells, many doctors are leery of putting them directly into patients until more research is done. But the cells could be immensely important in helping scientists understand and treat genetically based diseases.

By the time a full-blown disease has emerged, says Harvard stem-cell biologist Konrad Hochedlinger, it's like an airplane that has crashed. You can examine the wreckage for clues, but what you really want is the plane's black boxes?the flight-data and cockpit voice recorders that tell you exactly how electrical systems failed, hardware malfunctioned, and pilots made crucial errors. That's what doctors think iPS cells could provide. By coaxing some iPS cells into becoming the cell types affected in Huntington's disease, type 1 diabetes, or ALS (Lou Gehrig's disease), scientists will be able to watch in the lab as the disease unfolds. They'll be able to understand how the disease starts, which could lead to new ways of blocking it.

Embryonic stem cells are still regarded as the gold standard. That's why there is intense interest in the U.S. spinal-cord-injury trial. Sponsored by Geron Corp. in California, the trial will recruit patients within one to two weeks of their injuries, before scar tissue has formed. Doctors will inject a derivative of stem cells, called progenitor cells, that manufacture myelin, the substance that coats the long, spindly projections on nerve cells, much the same way that insulation coats electrical wires. Damage to cells that make and maintain the myelin sheath, as happens in spinal-cord injuries, prevents nerves from conveying messages from the brain. Although it's not clear yet whether the treatment is effective or safe, the restoration of even partial function would be a huge advance.

Geron's CEO, Dr. Thomas Okarma, thinks that spinal injury is a logical place to begin. Because patients will be completely paralyzed from the waist down, any improvement will be the result of the therapy, not chance. And the spinal cord is an "immune-privileged site," meaning that the attack cells of the immune system cannot get in and destroy the embryo-derived cells. "If the therapy is safe and effective, the potential impact will extend way beyond spinal-cord injury," says Okarma. "It will mark the start of a new era in medical therapeutics."

Other companies aren't waiting for the results. The U.S. pharmaceutical giant Pfizer is pursuing two other embryonic-stem-cell-based therapies, which it hopes to have in clinical trials by 2011. In April the company partnered with University College London to pursue a therapy for macular degeneration, the principal cause of blindness in the elderly. The disease leads to the gradual destruction of the macula, the sensitive central portion of the retina. But Peter Coffey, professor of cellular therapy and visual sciences at UCL, is using embryonic cells to make the same type of support cells that lie just behind the retina, providing it with nutrients. The goal is to implant a disc-shaped layer of the cells behind the retina. Immune rejection should not be a problem, since the eye is also immune-privileged.

Pfizer's other collaboration, with Novocell in California, aims to devise a treatment for some of the 100 million patients worldwide with insulin-dependent diabetes. Novocell is using embryonic stem cells to help regenerate all five of the pancreas's cell types. But there's a hitch. Unlike the eye or the spinal cord, the pancreas has no immune protection. For this, Novocell has devised a clever solution. It encases the stem-cell-derived progenitor cells in a capsule that can be implanted in the body. The pore size of the fabric is large enough to allow oxygen, glucose, and insulin to pass through but small enough to keep out big immune cells. "If problems should develop, the surgeon can easily remove the capsule," says Liz Bui, director of intellectual property for Novocell.

Some researchers aren't interested in just replacing impaired cells. They're using adult stem cells?which exist within organs to help with minor repairs?to grow entire replacement organs and tissues. Dr. Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest University in North Carolina, has made human bladders in this way. He starts by taking a small bladder biopsy from the patient and extracting his or her stem cells. After allowing the cells to multiply in the lab for about a month, he spreads them onto a collagen scaffold fashioned in the shape of a bladder. He then incubates the would-be organ in a bioreactor that provides the same temperature, oxygen level, growth factors, and nutrients that would be found in the body. In two weeks, he has a small but functional organ, ready for a patient.

In the early 2000s, Atala completed the procedure on seven children with spina bifida, who never developed fully functional bladders. He has now followed these patients for eight years to make sure there are no drastic failures or side effects. And he has moved on to other possible replacement parts. "We're working on 22 tissues and organs, including kidneys, heart valves, and cartilage," he says.

Because any new therapy is inherently risky, researchers are careful about creating false hopes that cures are just around the corner. Therapies that succeed in the idealized world of the lab can fail in real life or take decades to put into practice. As doctors and regulators begin to consider treating patients, they still have basic questions. Will the cells survive for long in the body? Will they integrate to form functioning tissue? Will the benefits outweigh risks that may become apparent only decades from now? Scientists are daring to hope, though, that after a decade of hype, real progress is imminent. Millions of patients worldwide could one day be the beneficiaries.

By Anne Underwood | NEWSWEEK

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Tuesday, December 16, 2008

Help Find A Cure for SCI!

By joining Find A Cure Panel?s exciting online research panel for people with spinal cord injuries, you will be empowered to share your personal experiences in vital research.

What's more, for each survey you complete a $10 donation is made directly to a worthy nonprofit organization in spinal cord injury research and support.

Registering is fast, free and your privacy is completely protected!

Registration Link: Find A Cure Panel

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Friday, November 21, 2008

Nose Cells May Heal Spinal Cord Injuries

People paralysed by spinal cord injuries could soon be "repaired" using cells from their own noses, say Otago University researchers.


The Health Ministry's ethics committee has just approved an application by the Spinal Cord Society to open the way for a clinical trial involving 12 patients, which could start next year.

The society's president, Noela Vallis, said there was no shortage of volunteers ready to take part.

"Some have already gone overseas out of a sense of frustration that they can't access it [the experimental treatment] here," Mrs Vallis said.

About 5000 Kiwis are in wheelchairs as a result of accidents - the highest rate of any country in the developed world.

Research director Jim Faed, who heads the the Spinal Cord Society's lab at Otago University, has spent five years developing laboratory methods for growing cells potentially useful for spinal cord injury repair.

His team is focusing on two promising cell types: one is a kind of adult stem cell produced by a patient's own bone marrow.

However, researchers are likely to begin trials using olfactory (scent receptor) cells from the patient's nose, injecting them into damaged spinal cord.

"The olfactory tissue in the nose is unique because it is the only place in the body where there is constant replacement of nerve cells throughout life," Dr Faed said.

"There is growing medical opinion that these cells can help overcome the blocks that prevent nerve cells regenerating after damage to the spinal cord."

The nasal tissue acts like "nurse cells", providing growth factor hormone to nerve cells, enabling them to make "meaningful connections".

Internationally, several research groups have done animal trials using the cells, but there has been only one human trial - in Portugal in 2006. The Otago group is in contact with Portuguese neuropathologist Carlos Lima, who pioneered that trial.

Dr Faed said some participants experienced side-effects, but they were "few and manageable" and none had been fatal.

Positive benefits for patients included return of some muscle function and sensation in parts of the body which previously had no feeling.

Dr Faed said the Dunedin lab hoped to get full approval for the trial before Christmas, and would then begin recruiting patients. The first 12 could start treatment next year.

Mrs Vallis - who founded the society after her late husband was paralysed in an accident - said the group aimed to raise $1 million to fund the trial, in addition to the $300,000 it finds every year to run the lab. "We should be at the forefront of developing this medical treatment, given the number of our citizens in wheelchairs."

Feilding man Iain Scott, a quadriplegic since dislocating his neck while playing rugby 19 years ago, said the possibility of the treatment was "huge" and gave hope to people with spinal cord injuries. "If nothing happens, at least you had a go ... you don't want to die wondering."

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Thursday, February 07, 2008

Could a Spinal "Bypass" Reverse Paralysis?

A breakthrough in spinal surgery yesterday offered hope to victims of paralysis.

The technique, which has been tested on rats, involves bypassing damaged tissue in the spine.

This allows signals to travel across injured areas, New Scientist reports.

Dr John Martin and his colleagues at Columbia University in New York have so far tested the procedure only on rodents. They selected a motor nerve branching from the healthy cord above the injury and cut it away from the abdominal muscle to which it is normally attached.

They then stretched the free end across the injured section of spinal cord and used a protein "glue" to fix it.

Two weeks later the team found that the graft had sprouted new extensions which had begun to form connections - or synapses - with the motor nerves in the isolated lower spine.

Zapping the spinal cord above the injury made the lower limbs of the rats twitch - showing motor signals had started once again to pass along the entire length of the spine.

The researchers say removing the nerve from the abdominal muscle did not appear to cause any major side effects and suggest this is because nearby nerves pick up the slack.

Fellow neuroscientist Dr Reggie Edgerton, of California University, said the approach had considerable clinical potential but added that it was too early to tell whether it would work in humans.

Dr Marie Filbin of the City University of New York cautioned that it may not be possible to "reprogramme" a nerve that normally connects to an abdominal muscle to transmit the sophisticated signals needed to produce fine, controlled movements.

But Dr Martin, who presented his study at the New York State Spinal Cord Injury Research Program Symposium, said: "What we want to do is plug in new connections to bypass the damaged region."

He believes that - with a little surgical assistance - spinal cord nerves above an injury could be capable of making such connections with nerves lower down the spine.

He said: "We know the nerves can make new connections to muscle so we asked whether it's possible for them to also connect with spinal cord neurons isolated through injury."

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Friday, August 24, 2007

Stem-cell therapy: Cure or hoax in China?

'Some get miracles'; others are skeptical

The website for Beike Biotechnology bursts with stories that can only be categorized as medical miracles: a paraplegic can move his legs again; a man with muscular dystrophy can carry a cup of water, a stroke victim can speak.

These tales of ailments treated come from all over the world - England, Hungary, Russia, Canada - and back the healing claims of a controversial Chinese treatment that purports to cure the incurable.

"I saw miracles every day I was there," says Leslie Wells, who flew to China in April, 11 years after a swimming pool accident rendered her arms and legs limp. "It can be a crapshoot. Some people get miracles, some people get nothing."

Doctors at Beike - based in Shenzhen, China - are treating a host of nerve disorders with stem-cell therapy, a procedure still under early clinical trials in much of the Western world. In just two years, doctors at Beike have injected stem cells from umbilical cords into the spines of nearly 1,000 patients from outside the country. Roughly 30 of those patients came from Canada, according to a Beike spokeswoman.

Approval for such treatments in Canada is years away, and the medical community here stands firmly opposed to people seeking them in China, citing possible health risks. In a research paper published in Neurorehabilitation and Neural Repair last year, several doctors in Canada and the United States followed up with patients of Hongyun Huang, who has been offering stem-cell treatments in China for several years. Few of the patients had improved since returning from China.

"If it sounds too good to be true, it's too good to be true," says Michael Rudnicki, Canada Research chair in molecular genetics at the University of Ottawa.

But increasing numbers of Canadians are sidestepping domestic regulations and venturing to China in hopes of a cure.

Ms. Wells, of Milton, Ont., first heard about Beike in a news story she read about two Ontario women who had suffered spinal-cord injuries in a car accident and then received the stem-cell treatments in China with some success.

As she flipped through the beaming testimonials on the company's website, it crossed her mind that the whole thing might be a scam. She just wanted a cure to nerve pain so crippling that "no painkiller known to man would help."

Her spine specialists warned her against it.

Eventually, she decided. "I was like, all right, what do I have to lose? Just a little money."

Ms. Wells paid $23,000 for the procedure and travelled to Nanshan Hospital in China, where she received six injections teeming with stem cells into her spinal fluid. Beike says the stem cells repair damaged nerves.

After her second injection, the pain that had made jobs and school seem impossible, was nearly gone.

"On a scale of one to 10, it went from like a nine down to a two. I haven't taken a single painkiller since."

She's not alone in her praise of the injections. With his speech and balance failing, George Arruda, an Ancaster, Ont., landscaper with ataxia, flew to Nanshan for four spine injections and two IV drips.

Ataxia is a progressive disorder that prematurely kills the nerve cells responsible for balance and co-ordination, and is one of the long list of neural conditions that Beike will treat. That list also includes epilepsy, ALS, cerebral palsy, spinal-cord injury and strokes,

Mr. Arruda knew it was an uncertain therapy, but his wife had recently given birth to a daughter. "I just wanted to be a healthy strong dad for her."

Before the trip, he could get around only with the aid of a walker. One night, about midway through his treatment, he was surprised to find himself walking to the bathroom unassisted.

"Immediately, I was about 20 per cent better," he says.

Since returning to Canada in February, he's had a relapse of symptoms. But he says that was probable considering the degenerative nature of ataxia. He's now looking at other stem-cell treatments.

Western medical experts chalk up the positive testimonials to the placebo effect. "We can give people a sugar pill and tell them it will get rid of all their pain and they'll insist that it works," Dr. Rudnicki says, "so I'm highly doubtful of testimonials. If I just spent $30,000 on a procedure, I would want to say it worked too."

Researchers at the University of Alberta are in the midst of studying the proliferating number of companies offering stem-cell cures. So far, they've discovered more than 30 based all over the world.

"The term stem cell has so much currency around the world right now," says Tim Caulfield, Canada Research chair in health law at the University of Alberta and member of a Canadian network of stem-cell researchers. "Even though the scientific community is deeply skeptical, people just associate the term with hope. It's a perfect area for quackery."

Eventually, Dr. Caulfield expects that researchers can use the University of Alberta study to make policy recommendations. "If there is fraud, we want to find it. The people going in for this are often tremendously sick and desperate. We want to ensure they are not being exploited."

Beike is open to the scrutiny. Patients are encouraged to post pictures and blog entries online documenting their time in China. Most depict a pristine hospital with cheery medical staff.

"Most of the doctors who work for us have been trained in Europe or the U.S.," says Kirshner Ross-Vaden, lead medical consultant with Beike's North American operations. "These are people who are leading the entire medical field. We have the nicest hospitals in China. The North American medical establishment is simply behind the times."

Beike says that 86 per cent of their clients show some measure of improvement.

Researchers in Canada say that while clinical trials have begun to look at the possibilities of stem-cell treatments, the therapies won't be available to the public for years - if they actually work.

Until that day comes, researchers here continue to advise against a stem-cell trip to China.

"They are ... putting patients at risk," Dr. Rudnicki says.

By: PATRICK WHITE

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Thursday, July 26, 2007

Spinal Cord Injury Therapy Developed

U.S. medical scientists have developed a new spinal cord therapy that helps the body permanently recover from such injuries.

Researchers at the Sloan-Kettering Institute for Cancer Research studied rats with crushed spinal cords. The scientists found treatment soon after injury, combining radiation therapy to destroy harmful cells and microsurgery to drain excess fluids, significantly helped the body repair the injured cord.

The scientists, led by Nurit Kalderon, said their findings demonstrate conventional clinical procedures hold promise for preventing paralysis due to spinal cord injuries. Currently there is no cure for human spinal cord injury.

"This research opens the door to developing a clinical protocol for curing human spinal cord injuries using conventional therapies," said Kalderon.

The study, supported by a grant from the National Institute of Neurological Disorders and Stroke, appears in the online journal PLoS One.

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