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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Friday, November 21, 2008

Nanotechnology for Spinal Cord Injury

A cure for spinal injuries that leave people paralyzed, currently incurable, is being developed by Researchers at Northwestern University in Chicago. They are looking into using new nanotechnology that could enable them to completely heal cut and severed spinal cords allowing the previously paralyzed to walk again.

Spinal cord injury often leads to permanent paralysis and loss of sensation below the site of the injury due to damaged nerve fibers which can?t regenerate. These nerve fibers (axons) have the capacity to grow but don?t because they are blocked by scar tissue that have developed around the injury. Northwestern University researchers have shown that a new nano-engineered gel inhibits the formation of scar tissue at the injury site and enables the severed spinal cord fibers to regenerate and grow.

The gel is injected as a liquid into the spinal cord and self -assembles into a scaffold that supports the new nerve fibers as they grow up and down the spinal cord, penetrating the site of the injury. When the gel was injected into mice with a spinal cord injury, after six weeks the animals had a greatly enhanced ability to use their hind legs and walk.

However it was stressed that the results were preliminary and there is no magic bullet and it may not necessarily work on humans, but it helps a new technology to develop treatments for spinal injuries.

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Sunday, July 20, 2008

Stem Cells Identified for Spinal-Cord Repair

A researcher at MIT?s Picower Institute for Learning and Memory has pinpointed stem cells within the spinal cord that, if persuaded to differentiate into more healing cells and fewer scarring cells following an injury, may lead to a new, non-surgical treatment for debilitating spinal-cord injuries.

The work, reported in the July issue of the journal PLoS (Public Library of Science) Biology, is by Konstantinos Meletis, a postdoctoral fellow at the Picower Institute, and colleagues at the Karolinska Institute in Sweden. Their results could lead to drugs that might restore some degree of mobility to the 30,000 people worldwide afflicted each year with spinal-cord injuries.

In a developing embryo, stem cells differentiate into all the specialized tissues of the body. In adults, stem cells act as a repair system, replenishing specialized cells, but also maintaining the normal turnover of regenerative organs such as blood, skin or intestinal tissues.

The tiny number of stem cells in the adult spinal cord proliferate slowly or rarely, and fail to promote regeneration on their own. But recent experiments show that these same cells, grown in the lab and returned to the injury site, can restore some function in paralyzed rodents and primates.

The researchers at MIT and the Karolinska Institute found that neural stem cells in the adult spinal cord are limited to a layer of cube- or column-shaped, cilia-covered cells called ependymal cells. These cells make up the thin membrane lining the inner-brain ventricles and the connecting central column of the spinal cord.

?We have been able to genetically mark this neural stem cell population and then follow their behavior,? Meletis said. ?We find that these cells proliferate upon spinal cord injury, migrate toward the injury site and differentiate over several months.?

The study uncovers the molecular mechanism underlying the tantalizing results of the rodent and primate and goes one step further: By identifying for the first time where this subpopulation of cells is found, they pave a path toward manipulating them with drugs to boost their inborn ability to repair damaged nerve cells.

?The ependymal cells? ability to turn into several different cell types upon injury makes them very interesting from an intervention aspect: Imagine if we could regulate the behavior of this stem cell population to repair damaged nerve cells,? Meletis said.

Upon injury, ependymal cells proliferate and migrate to the injured area, producing a mass of scar-forming cells, plus fewer cells called oligodendrocytes. The oligodendrocytes restore the myelin, or coating, on nerve cells? long, slender, electrical impulse-carrying projections called axons. Myelin is like the layer of plastic insulation on an electrical wire; without it, nerve cells don?t function properly.

?The limited functional recovery typically associated with central nervous system injuries is in part due to the failure of severed axons to regrow and reconnect with their target cells in the peripheral nervous system that extends to our arms, hands, legs and feet,? Meletis said. ?The function of axons that remain intact after injury in humans is often compromised without insulating sheaths of myelin.?

If scientists could genetically manipulate ependymal cells to produce more myelin and less scar tissue after a spinal cord injury, they could potentially avoid or reverse many of the debilitating effects of this type of injury, the researchers said.

Provided by MIT

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Thursday, July 17, 2008

Allen Institute Releases Spinal Cord Map

Spinal cord injuries have long baffled doctors. Now the Allen Institute for Brain Science is doing for spinal research what they did for brain science - providing the first comprehensive road map of a mouse's spine.

"It's a groundbreaking project that tells us where each gene in the genome is turned on in cells in the spinal cord," Dr. Allan Jones, Allen Institute's Chief Scientific Officer, said in a news conference Thursday. "This is very important because the genes ultimately contribute to the specific biochemistry of a particular cell."

Jones says because mice share many of the same genes with humans, the implications are far-reaching.

"Researchers working on things like spinal muscular atrophy, degenerative disease like MS and Lou Gerhig's disease or ALS , also people who suffer from spinal cord injuries," he said.

The first 2,000 genes are available online now, with the full map of 20,000 genes to be completed by the end of the year. All the information is free to scientists and the public.

"It's sort of a virtual microscope that scientists can come and zoom in," said Jones. "It's like having the microscope slide right there in front of them."

"The comprehensive map of the genes of the spinal cord will be an incredible resource for scientists and researchers studying how the spinal cord is altered in disease or an injury, and more importantly it's going to give hope to really millions of Americans who suffer from spinal cord diseases and disorders," Sen. Patty Murray said at the news conference.

Said each day, 1,000 scientists have been accessing the Allen Brain Atlas Project, which went live in December of 2004 and was completed in 2006.

"Researchers have been using this to support all aspects of brain research," said Jones. "Just some examples: Alzheimer's, autism, bipolar, Down syndrome, Fragile X mental retardation, epilepsy, alcoholism, obesity, Parkinson's disease, sleep, hearing, memory, and more."

In December, Marine Corporal Jerold Mason was paralyzed in a car crash. These days he's grateful for the small things, like being able to listen to his I-Pod.

"It like takes you away from the stress. I will always use music to do that," he said.

Mason can now control his I-Pod with a straw. This one small step is inspiring him.

"Allows me to think of times when I did have the use of my arms, my legs and you know it makes me want to push harder," he said.

Thanks to the spinal cord map, researchers will be able to push harder, as well.

"It's all undiscovered new stuff. So they're a bit like a kid in a candy store in terms of the new data in the excitement of looking at it," said Jones.

Microsoft co-founder Paul Allen started the mapping project with $100 million in seed money. It's now grown to include other private, as well as public, funding.

Story By JEAN ENERSEN

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Wednesday, April 30, 2008

Decompression Aids Spinal Injury Recovery

Done within 24 hours, the procedure improved neurological outcomes a year later


Surgical decompression of the spinal cord involves the removal of various tissue or bone fragments that are being squeezed and comprising the spinal cord. While commonly done after an injury occurs, the timing of the procedure varies widely.

The study looked at 170 patients with cervical spinal cord injuries, graded as A (most several neurological involvement) to D (least severe), who underwent decompression surgery.

Six months after the surgery, 24 percent of the patients who had the surgery within 24 hours showed two-grade or greater improvement in their condition compared with only 4 percent in the group that had the surgery more than a day later.

"The initial results suggest that decompression within 24 hours of injury may be associated with improved neurological recovery at one-year follow-up. However, further recruitment of patients with long-term follow-up is necessary to validate these promising results," study author Michael Fehlings, head of the Krembil Neuroscience Center at the University Health Network in Toronto, said in a prepared statement.

Fehlings was expected to present the findings in Chicago April 28 at the annual meeting of the American Association of Neurological Surgeons.

Every year, almost 12,000 people in the United States and Canada, mostly young adults, sustain a spinal cord injury. Although surgery, such as decompression, can help, these procedures often do not dramatically improve overall recovery and outcome.

"This is an area of medicine that has not seen tremendous scientific advances, so there remains an urgent need to improve upon current interventions to help restore neurological function in patients with acute (spinal cord injury)," said Fehlings, who is also professor of neurosurgery at the University of Toronto.

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Friday, April 18, 2008

New Discovery May Aid Treatment of Spinal Cord Injuries

A discovery by researchers at University of Minnesota may provide new insights into how the spinal cord controls walking, and this may pave the way for developing treatments for diseases of the central nervous like Parkinson?s disease and spinal cord injuries.

Led by Joshua Puhl, Ph.D., and Karen Mesce, Ph.D., in the Departments of Entomology and Neuroscience, the study has found a possibility that the human nervous system, within each segment or region of spinal cord, may have its own unit burst generator to control rhythmic movements such as walking.

The researchers chose to study a simpler model of locomotion in the medicinal leech, and this uncovered the residing spots of these unit burst generators and it also showed that each nerve cord segment has a complete generator.

It was discovered that a neuron triggers to set off a chain reaction that gives rise to rhythmic movement and the moment those circuits are turned on, the body essentially goes on autopilot.

The researchers mainly focused on the segmented leech for study as they have fewer and larger neurons, making them easier to study.

For most of us, we can chew gum and walk at the same time. We do not have to remind ourselves to place the right leg out first, bring it back and do the same for the other leg. So how does the nervous system control rhythmic behaviors like walking or crawling, said Mesce.

The study also discovered that dopamine, a common human hormone, can turn each of these complete generator units on.

Because dopamine affects movement in many different animals, including humans, our studies may help to identify treatments for Parkinsons patients and those with spinal cord injury, said Mesce.

The study was published online in the Journal of Neuroscience.

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Tuesday, April 08, 2008

Nanotechnology May Help Reconnect Nerves

U.S. researchers say they have created a nano-engineered gel that can enable severed spinal cord fibers to regenerate and grow.

Mice paralysed by spinal injuries have been able to walk again thanks to a treatment developed by scientists in the US. The therapy uses proteins that self-assemble into nano-fibers at the site of the injury, encouraging nerves to regrow.

Spinal cord injuries often lead to permanent paralysis and loss of sensation because the damaged nerve fibers can't regenerate, Northwestern University scientists said. Although nerve fibers or axons have the capacity to re-grow, they don't because they're blocked by scar tissue that develops around the injury.

The nanogel developed at the university's Feinberg School of Medicine inhibits formation of scar tissue and enables the severed spinal cord fibers to regenerate and grow, the scientists said.

The gel is injected as a liquid into the spinal cord and self-assembles into a scaffold that supports new nerve fibers. When the gel was injected into mice with a spinal cord injury, after six weeks the animals had a greatly enhanced ability to use their hind legs and walk.

"It's important to understand that something that works in mice will not necessarily work in human beings," said study leader Dr. John Kessler, who noted that if the gel is eventually approved for humans, a clinical trial could begin within several years.

The research is reported in the Journal of Neuroscience.

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Sunday, February 17, 2008

Spinal Cord Injury Regeneration Hope

Scientists believe they are close to a significant breakthrough in the treatment of spinal injuries.

The University of Cambridge team is developing a treatment which could potentially allow damaged nerve fibers to regenerate within the spinal cord.

It may also encourage the remaining undamaged nerve fibers to work more effectively.

Spinal injuries are difficult to treat because the body cannot repair damage to the brain or spinal cord.

Although it is possible for nerves to regenerate, they are blocked by the scar tissue that forms at the site of the spinal injury.

Scientists believe they are close to a significant breakthrough in the treatment of spinal injuries.

The Cambridge team has identified a bacteria enzyme called chondroitinase which is capable of digesting molecules within scar tissue to allow some nerve fibers to regrow.

The enzyme also promotes nerve plasticity, which potentially means that remaining undamaged nerve fibers have an increased likelihood of making new connections that could bypass the area of damage.

Boosts rehabilitation

In preliminary tests, the researchers have shown that combining chondroitinase with rehabilitation produces better results than using either technique alone.

However, trials have yet to begin in patients.

Lead researcher Professor James Fawcett said: "It is rare to find that a spinal cord is completely severed, generally there are still some nerve fibers that are undamaged.

"Chondroitinase offers us hope in two ways; firstly it allows some nerve fibers to regenerate and secondly it enables other nerves to take on the role of those fibers that cannot be repaired.

"Along with rehabilitation we are very hopeful that at last we may be able to offer paralyzed patients a treatment to improve their condition."

'Ground-breaking'

Dr Yolande Harley, of the charity Action Medical Research which funded the work, said: "This is incredibly exciting, ground-breaking work, which will give new hope to people with recent spinal injuries."

Paul Smith, of the Spinal Injuries Association, said medical advances meant that spinal injuries had ceased to be the terminal conditions that they often once were, but they still had a huge impact on quality of life.

However, he warned against raising expectation before the treatment was fully tested on patients.

He said: "What often happens in a clinical setting is that you don't get to see the results you would have liked."

In the UK there are more than 40,000 people suffering from injuries to their spine, which can take the form of anything from loss of sensation to full paralysis.

The average age at the time of injury is just 19.

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Wednesday, November 28, 2007

Scientists Identify Gene that Helps Salamanders Regrow Limbs

University of Montreal researchers have identified a gene that allows limb regeneration in the axolotl, a salamander that lives in Mexican lakes.

The gene, called TGF-beta 1, controls the generation and movement of new cells, and allows the axolotl to regrow complex structures like limbs, tail, jaw, spinal cord and even parts of its brain.

Humans also have this gene. The difference is that in humans, instead of telling a limb to regenerate, the gene tells the wounded area to heal and form a scar. If scientists can find a way to manipulate TGF-beta in humans, it could lead to the ability to regrow organs and limbs, as well as treatments for spinal cord injury and severe burns.

In the study, the scientists used a drug that inhibited the gene in axolotls. The treated axolotls couldn't regrow their limbs, proving that TGF-beta plays a role in regeneration.

The salamander study is published in the November 28 issue of PLoS ONE.

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Wednesday, November 07, 2007

New Clinical Trials Could Open "Golden Era" In Spinal Cord Injury

New experimental therapies are being -- or soon may be -- tested in clinical trials that could open the doors to a "golden era" for research to improve the treatments of people with spinal cord injuries, brain injuries, stroke, and other severe movement disorders, scientists say.

"The studies highlighted here reflect decades of basic science research that have led to some measure of understanding the events taking place in traumatic neural injury and disease, and how these events can be modulated to improve function," says Aileen Anderson, PhD, of the University of California, Irvine.

"As a result of this work, we have the exciting opportunity to begin testing these pathways in the clinical setting in an attempt to minimize the progression of damage and, in some cases, perhaps repair it," says Anderson.

The new therapies include an experimental, custom-made antibody to NOGO-A, one of several inhibitory proteins for nerve fiber growth that are produced naturally in the human spinal cord and brain. It soon will be evaluated as a therapy for patients who are newly paralyzed from spinal cord injury.

This Phase I clinical trial, conducted by the European Network of Spinal Cord Injury Centers, follows extensive laboratory research on NOGO-A, as well as animal tests of the experimental monoclonal antibody's effectiveness in neutralizing the inhibitory protein.

NOGO-A is one of several proteins whose existence in the adult body helps to explain our limited ability to grow new brain and spinal cord tissue in response to injury or disease, says Martin Schwab, PhD, of the Brain Research Institute at the University of Zurich in Switzerland. These inhibitory proteins, which are silent during embryonic and fetal development and even during the first few months of an infant's life, vigorously limit the inherent ability of adult brain and spinal cord neurons to regrow fibers that have been cut by injury.

"As a result, neurons as well as their axons retain a low growth potential following brain trauma or spinal cord injury," Schwab says. Axons transmit from neurons the electrical impulses that underlie our ability to move our arms and legs.

To restore fiber-growing ability to the brain and spinal cord, Schwab first prevented NOGO-A from fulfilling its function as an inhibitor of fiber growth and regeneration in laboratory animals. He showed that the anti-NOGO-A antibody allowed fiber tracts of the rats' damaged spinal cords to regenerate partially, thereby restoring some motor function.

"Animals treated with such reagents showed molecular changes which strongly suggest that the growth machinery of the nerve cells is turned on, similar to the situation during development," Schwab says. Anatomical studies showed that the antibody treatment induced long-distance regeneration and the formation of new circuits.

"Nerve fiber tracts that were not directly affected by the injury also sprouted after treatment," Schwab says. These physical changes restored some of the animals' leg movement, a "remarkable behavioral recovery," he adds. "Many animals showed almost full recovery in sensory as well as motor tests." The untreated, or control, animals in the study remained severely impaired.

"The coming few years will show whether the step from bench to bedside can be successfully achieved in spinal cord injury and central nervous system trauma without the danger of serious side effects or complications," Schwab says.

In another presentation, Michael Fehlings, MD, PhD, of the Toronto Western Hospital and University of Toronto described several current or planned clinical trials for treating spinal cord injury. Immediate treatment may not only reverse the initial damage to the spinal cord but also may minimize secondary injury, potentially sparing the patient additional neurological problems, Fehlings says.

The prospective clinical study, titled STASCIS, which is evaluating the role and timing of early decompressive surgery in patients with cervical spinal cord injury, has to date enrolled more than 240 patients. The study, he says, is based on the premise that within hours of a spinal cord injury, a patient should be undergoing surgery that will reduce pressure on the cord in order to limit damage to it and surrounding tissues. Initial evaluations of the clinical trial data have indicated that immediate surgery is safe and feasible and, by reducing the pressure on a compressed spinal cord, may encourage the recovery of function.

In another clinical trial, scientists soon will determine whether the Food and Drug Administration-approved medication riluzole protects nerve cells and promotes functional recovery when it is administered after spinal cord injury. Riluzole, now used to treat people with amyotrophic lateral sclerosis (ALS), prevents neurons from releasing too much sodium. In lab animal studies, the drug was neuroprotective.

In other animal model studies, the drug CethrinŽ has been found to lessen post-traumatic neural cell death. To evaluate the safety of this recombinant protein drug and obtain preliminary efficacy data in human patients, Fehlings and colleagues at nine centers in the United States and Canada administered the agent topically to 37 patients with complete cervical and thoracic spinal cord injury. "The drug shows a high degree of safety and promising clinical neurological improvements after one year of follow-up," he says.

"While the results of a single arm, uncontrolled study need to be interpreted cautiously, this level of improvement exceeds rates of spontaneous neurological recovery," Fehlings says. A prospective, randomized placebo-controlled efficacy trial is planned for early 2008.

The Fehlings team has completed studies in lab rodents in which neural stem cells were transplanted following spinal cord injury. The stem cells, programmed to restore the myelin layer around spinal cord nerve fibers, promoted significant neurological recovery. This strategy shows considerable promise for translation into the clinic, Fehlings says.

If it continues beyond a critical time point, the medical practice of treating spinal cord-injured patients with immune suppressive drugs as soon after the injury as possible may hinder rather than promote recovery, according to studies by Michal Schwartz, PhD, of the Weizmann Institute of Science in Rehovot, Israel.

"For many decades, the detection of immune cells in the injured brain or spinal cord was interpreted to represent part of the pathological process that occurs following injury and prevents healing," Schwartz says. "This dogma was so well ingrained that the common practice in Western countries has been to treat patients who experienced spinal cord injury with immune suppressive drugs as early as possible following the injury."

However, Schwartz's laboratory showed that the immune system is required for protection, repair, and renewal of the brain and spinal cord following acute or chronic damage. But, she says, "to achieve beneficial results, immune-cell involvement in repair must be critically controlled in terms of the timing, nature, intensity, and duration of activation."

A beneficial immune response involves not only the activity of immune cells residing in the damaged tissue, but also the timely recruitment of immune cells from the blood. These blood-borne immune cells home to a precise location around the injured site, where they sense the tissue damage and secrete factors needed to induce repair.

"This timely recruitment of immune cells to the site of injury, and their well-controlled activation, is an essential stage in the multistep process of brain and spinal cord repair," Schwartz says. "Curtailing this process by suppressing, rather than modulating, the immune response deprives the tissue of its most powerful physiological repair mechanism."

Schwartz designed and tested several immune-based therapeutic approaches for promoting spinal cord repair. One was a vaccine containing a peptide derived from a protein that resides in the injured tissue and that can boost immune response by activating a particular population of immune cells, the T lymphocytes. T lymphocytes specifically recognize proteins that are associated with the injury.

Pairing the vaccine with an injection of neural stem cells resulted in a synergistic effect on recovery. "Surprisingly, however, the injected stem cells did not themselves give rise to new neurons but rather promoted the formation of new neurons from the tissue's resident stem cells," Schwartz says.

Scientists also have found in work with laboratory animals that when human stem cells are transplanted into the body, they form active synapses with the animal's own neurons for limb movement. After they were implanted, the human stem cells developed into neurons and made local connections with spinal cord motor neurons but they did not project to the animals' peripheral nerve and hind limb muscles, says Vassilis Koliatsos, MD, of Johns Hopkins University.

Koliatsos conducted this study with rodents affected by a genetic form of ALS, which is characterized by the progressive degeneration and death of motor neurons. "These findings demonstrate that grafted human neural stem cells become synaptically incorporated into the motor circuitry of ALS rats," Koliatsos says.

The exact role of these new synapses, which are specialized junctions through which neurons signal each other, is not yet defined. Koliatsos says that they may serve to communicate physiological signals pertaining to limb movement or, more likely, to transfer nourishing chemicals from neural stem cells to the degenerating or vulnerable motor neurons of the host ALS animal.

The transplanted human stem cells produced an abundance of two key nourishing chemicals for motor neurons: glial cell-derived neurotrophic factor and brain-derived neurotrophic factor (BDNF), which, Koliatsos says, "may be the main factor behind the therapeutic effect of neural stem cell grafts."

In the latest study, the implanted human neural stem cells, obtained from a 2-month-old human fetal spinal cord, were transplanted into the spinal cord of ALS rats when they were 9 weeks old.

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Thursday, September 06, 2007

Spinal Cord Implant

A team at University College London (UCL) is developing a spinal canal implant that could improve the quality of life and life expectancy for people with serious spinal cord injury.

Previous research has restored function to this patient group by stimulating muscles through the skin using surface electrodes or implanting electrodes in the muscles or between the spinal cord and the muscles.

UCL has for some time been investigating a different approach by putting the electrodes on the nerve roots, which is where the nerves emerge from the spinal cord but remain within the spinal canal.

'These are relatively fine and fragile fibres within the spinal canal,' said Prof Nick Donaldson of UCL's neuroprosthesis engineering department. 'The complication is that there are many fibres very close together which emerge from the spinal canal and form the major nerves that run down into the legs and also control the bowel and bladder.

'The advantage from a surgical point of view is that they're all available in one location, so you can, in a single procedure, field and place the electrodes together rather than having to fit electrodes and route cables over the legs of the patient.'

FineTech Medical makes an implant called the sacral anterior root stimulator for this site in the body which is just used for neurological functions ? primarily emptying the bladder and bowel.

'That has been very successful and made a big difference to patients who've had it fitted,' said Donaldson, 'but it doesn't do anything for the legs. I ran a research project in the 1990s where we stimulated the roots a bit higher up ? the lumbar roots ? and showed that we could get useful leg function, allowing a paraplegic to propel a recumbent cycle.

'We would like to expand the existing device by giving it more channels so we can add leg function to the existing neurological functions of the implants.'

The surgeon inserting the implant has to connect very small electrodes to individual nerve roots in such a way that the currents which flow between the electrodes just stimulate the target nerve roots, not neighbouring ones. This is achieved using a structure called an 'active electronic book,' because the surgeon can place the roots between the 'pages' of the device, separating them.

'The project, which is mainly technological, addresses how we can increase the number of stimulation channels without having many cables going into the spinal canal, said Donaldson. 'At the moment we have really been working at the limit of what the surgeons think is practical, with 12 channels, each corresponding to a nerve stimulated. The number one might want to stimulate is in the region of 20 to 30, so if we could double or treble the number of channels, we could do more for patients.

'That requires us having some way of putting the electronics right down near the electrodes. So the idea of the active book is that it has semiconductor switches and perhaps amplifiers within the electrode structure, we call the book and relatively few wires going through the dura (the outer membrane of the spinal cord) into the canal.'

This has the advantage of reducing the risk of infection and cerebro-spinal fluid (CSF) leak.

By the end of the project, the team hopes to show the technology can run in saline for long periods. It aims to demonstrate a method of sealing the electronics so the implant will be reliable for years, and carry out mechanical tests to prove its robustness.

The EPSRC-funded project runs from 2008 until 2010 during which time UCL will carry out the design of the electronics. When complete, approval will be sought from the Medicines and Healthcare products Regulatory Agency (MHRA) to undertake trials, which could take up to 10 years

UCL's project partners are the Tyndall Institute, which will develop the integrated circuit sealing, and Freiberg University, which has special knowledge of laser cutting tiny electrodes.

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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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Wednesday, May 30, 2007

MRI Predicts Spinal Cord Injury Recovery

MRI imaging is giving neurosurgeons good insight into whether patients with serious spinal cord injuries can recover, a new study shows.

Within 48 hours of the injury, these images should be able to provide a reasonable prediction of a patient's fate, Canadian researchers reported n the June issue of the journal Radiology.

Currently, MRIs are commonly but inconsistently performed on spinal cord injury patients, noted study co-author Dr. Michael G. Fehlings, professor of neurosurgery at the University of Toronto. In light of the study results, they should become the "standard of care, unless pressing medical circumstances preclude the test from being done," he said.

The U.S. National Spinal Cord Injury Association estimates that between 250,000 to 400,000 Americans now have spinal cord injuries or other spinal cord problems. Motor vehicle accidents are responsible for about 44 percent of spinal cord injuries in the United States.

In the new study, Fehlings and colleagues examined 100 patients -- 79 men and 21 women -- with severe spinal cord injuries, mostly as a result of motor vehicle accidents. The patients underwent MRI scans that "allow doctors to see the site of spinal cord injury and to appreciate whether the spine is fractured and whether there is pressure on the spinal cord," Fehlings said.

His team found that three factors -- severity of spinal cord compression, bleeding and spinal cord swelling -- were directly connected to poor outcomes. Essentially, the factors indicate "a more severe injury with less opportunity for recovery," Fehlings said.

But the prognosis was good for patients without these symptoms, even if they were severely injured.

In addition to predicting the likelihood of recovery, MRI images can help doctors determine whether patients should undergo spinal cord decompression surgery, Fehlings said.

There is, of course, a potential downside to a bleak prediction: It could leave patients with little hope for the future. But Fehlings said that's not necessarily so.

"Communication with patients is an art. It is important for physicians to communicate a sense of hope even in the setting of a severe spinal cord injury," he said.

From another perspective, one doctor said it's important for patients "to understand the bleakness of the future" if there are signs of those factors discussed in the study.

"Better to know than to be given false hope," reasoned Dr. Robert Quencer, a radiologist at the University of Miami/Jackson Memorial Medical Center.

By Randy Dotinga

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Tuesday, May 01, 2007

Doctors Try New Injection To Fight Paralysis

There are currently no effective therapies for spinal cord injuries. But a protein injection may help some patients walk again.

Two years ago, Michelle Robinson was on her way home from work when she was hit by a car.

"All I remember is hearing a loud screeching noise and I remember going, flying up in the air," Michelle said.

The accident left the 42-year-old mother paralyzed. Now she hopes an experimental drug will put her back on her feet.

"It appears that this actually does improve their prognosis," said James Harrop, a neurosurgeon.

Harrop is testing the novel drug called Cethrin to treat spinal cord injuries.

"It's a paste or a jelly that you sort of just spread onto the spinal cord with a little applicator, like a syringe," he said.

Doctors apply the protein during standard decompression surgery to stabilize the spine. The idea is to stop nerve cell death that includes days to weeks after the injury occurs.

"Inside the cell, there?s a nucleus which is controlling sort of this, the auto-regulator of the cell and what it?s doing is it?s telling the cell we don?t want you to function anymore," Harrop said.
Cethrin is designed to interfere with that message by seeping through the spinal cord membrane to cells at the injury site.

"It goes into the cell and it says 'wait a minute'. I don't want you guys going down that path anyways, I want you to stop and I want you to start repairing the cell," Harrop said.

Early trials show the protein therapy is safe. And the results are promising. Michelle says she is both excited and hopeful the new therapy will work for her.

"I say those words because Dr. Harrop told me that he was very hopeful that, you know, maybe one day I would be able to walk again, so I'm very hopeful also."

Doctors caution that Cethrin, also called BA210, is not a magic bullet. But in the study, 31 percent of patients regained some function after being injected with the drug. The study is still enrolling patients. About 253,000 Americans are living with a spinal cord injury. Roughly 11,000 new cases occur every year.

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Monday, April 09, 2007

Hospital Tests New Surgery

Baumont procedure could improve bladder control

What does it take to import a medical procedure from China to Detroit?

In a reversal of the globalization seen in many industries, doctors from Beaumont Hospital in Royal Oak this week began a pilot study, under the watchful eye of the Chinese surgeon who developed the operation, that could help millions of Americans regain bladder control after spinal cord injuries and spina bifida, one of the most common and disabling birth defects.

Beaumont's team will perform the procedure on seven children and one adult with spina bifida, all but one of whom are from outside Michigan, evidence of the far-reaching appeal of the technique.

Then the team will wait one to two years to see if new nerve paths created in the surgery restore continence in the patients. Only then would the study be resumed.

Spinal cord patients, some 260,000 in the United States alone, and another 70,000 Americans who live with spina bifida await results.

The surgery creates a neural connection that signals the bladder to empty when a person touches the thigh, said Dr. Chuan-Gao Xiao, who practices at Huazhong University of Science & Technology in Wuhan, China.

If successful, the operation might save billions of dollars in lifelong costs related to incontinence and infection.

"We have over 200 children from all over the country who want this done and we have no other money right now," said Dr. Kenneth Peters of Beaumont's urology team and head of the team that traveled to China to learn the surgery. Applications poured in after the first three surgeries were performed at Beaumont in December on two people with spinal cord injuries and one with spina bifida. Without federal or private research grants that pay for many studies of investigational procedures, Beaumont had to find a donor.

J. Peter and Florine Ministrelli of West Bloomfield, who have given $15 million to the hospital for urology and cardiology research, will pay for this week's operations, which are estimated at $40,000 each.

Jessica Palmer, 8, who lives in Downingtown, Pa., underwent the procedure Tuesday. She is a medical pioneer already. When her mother was pregnant, doctors performed in-utero surgery to try to correct her spina bifida after it was diagnosed by an ultrasound test.

The Palmers say the pre-birth surgery did some good; Jessica walks with braces and is a bright second-grader who loves to draw and ride horses. "We were told she'd never walk," said her mother, Carol, a registered nurse.

"She's a tough little girl; she's been through so much already," said John Palmer, Jessica's father. The family considered going to China for the surgery. Though some risks are associated with it, "there's no guarantee with anything," Carol Palmer said.

There are no good estimates on the cost of incontinence in patients with spina bifida or spinal cord injury. The United States spends $16.3 billion a year on costs for urinary incontinence, according to a 2001 analysis in Obstetrics and Gynecology, a leading journal.

After several years of operating on animals, Xiao began performing the operation on humans with spinal cord injuries in 1995. He began doing the surgery on spina bifida patients in 2000, he said. In all, he's performed 340 surgeries, and says 80% have achieved satisfactory bladder control and no longer must use catheters. Some also have achieved bowel improvements, he said.

Children show regenerated nerves the fastest, he said. Those with prior bladder augmentations are not candidates for the operation.

Early on, two spina bifida patients developed muscular weakness and foot drop after the surgery, but changes in the technique have "dramatically decreased the incidence of this complication," Xiao said.

While he was doing a fellowship in Norfolk, Va., some of his research was underwritten by the Paralyzed Veterans of America and the National Institutes of Health, he said.

The surgery, called a hemi-laminectomy, is performed under general anesthesia and takes about two hours.

Doctors make about a four-inch incision near the lower part of the spine and open the dura, the protective sheath around the spinal cord, exposing the network of nerve roots that feed it. They find what they call a donor nerve in the leg, and measure its nerve conductivity with electrical tests.

The nerve then is split, with a portion still attached to the spinal cord, and routed to the bladder. There, another so-called recipient nerve from the spinal cord is spliced, again leaving a portion attached to the spinal cord, and the two ends are sewn together with a single stitch. It creates a new circuit that bypasses the brain, Peters said. "You are rerouting the nerve, using the nerve that moves the leg to feed nerves to the bladder."

Xiao compared the operation to fixing an electrical problem. Sometimes the lightbulb needs to be replaced; other times, the circuitry is the culprit, he said.

"What we are doing is putting the electricity back," he said.

BY PATRICIA ANSTETT

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Saturday, March 10, 2007

Scientists plan China, HK, Taiwan Stem Cell Trial

Scientists are preparing for a large clinical trial in 2008 which aims to use stem cells to help 400 patients with spinal cord injuries in Hong Kong, mainland China and Taiwan grow new cells and nerve fibers.

Stem cells from umbilical cord blood will be injected into the spinal cords of the participants, who will also be given lithium to help stimulate cell regeneration, said Wise Young, a leading neuroscientist and spinal cord injury researcher.

"What we'd like to do is study a broad range of patients, not just (those with) complete (spinal cord injuries)," said Young, professor at Rutgers' department of cellbiology and neuroscience. Rutgers is the state university in New Jersey in the U.S.

Researchers are now giving lithium to 20 patients in Hong Kong in the phase 1 safety and feasibility trial. Lithium is a chemical element that is believed to boost cell regeneration.
In preparation for the large 2008 trial, which will involve 400 patients in 14 mainland Chinese cities, Hong Kong and Taipei, doctors in all three places recently agreed on the method to deliver stem cells into spinal cords, said Young, who is also a visiting professor at the University of Hong Kong.

Stem cells extracted from matching umbilical cord blood taken from public blood banks will be injected into the spinal cords of the subjects, who will also be given lithium.

The procedure should hopefully help subjects grow new nerve fibers and "bridges" -- structures that allow the new fibers to reconnect with other parts of the spinal cord.

"Our main outcome measure will be neurological motor and sensory scores," Young said in an interview with selected media. "We want to see whether the patients recover sensation. It has three measures: touch, pain which is assessed by pin-prick, and the third is strength of 10 standardized muscles."

The trial, the biggest in the field in Asia, comes as China is devoting significant resources into stem cell research.

Its attitude and achievements have drawn U.S.-based scientists like Young to conduct research there due to opposition to embryonic stem cell research in the United States.

Opponents of embryonic stem cell research, including President George W. Bush, say it is unethical to experiment on human embryos, even those never destined to become a baby.
Stem cells are the body's master cells, found throughout the tissue and blood. Whether from the adult or from embryos, they may be used to find treatments and cures for serious diseases such as cancer and diabetes.

Embryonic stem cells are considered potentially the most powerful but are also the most controversial, and federal law greatly restricts the use of taxpayer money to pay for experiments using them.

"Scientists in the U.S. are so upset at the stopping of (embryonic) stem cell research, but this would be a great opportunity for Asia, great opportunity for China ... because there are so many researchers working in this field," Young said, adding that Hong Kong had a special position in all of this.

"Hong Kong is in a special position for science because it has credibility. Many people don't trust what is going on inside China," he said, noting also that Hong Kong badly needed government support and funding.

Private donors are funding the US$26 million spinal cord clinical trial.

By Tan Ee Lyn HONG KONG, Reuters

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