Monday, July 24, 2006

Spinal Cord Injuries Improved Years Later with Patients' Own Olfactory Cells

A team of researchers from Hospital de Egas, Lisbon, Portugal and Wayne State University Medical School in Michigan, USA, have shown that stem cells taken from the olfactory mucosa can be used successfully to treat spinal cord injuries, even years after the injury occurred.

A report published by the American Paraplegia Society says that seven patients, ranging in age from 18 to 32 years, who suffered severe spinal cord injuries as much as six and half years before, were treated with stem-like progenitor and ensheathing cells derived from the olfactory mucosa.

The cells were cultivated and engrafted onto lesions on the patients' spinal cord. Subsequent MRI scans showed "moderate to complete filling of the lesion sites." The report says that two patients experienced return of sensation in their bladders and one a return of limited anal control. All the patients experienced some improvement in motor abilities.

The olfactory mucosa is the region of the nasal passage where highly specialized cells detect odours. The olfactory ensheathing cells have been found to behave in much the same way as stem cells from more traditional sources such as bone marrow, but are easier to obtain.

In 2005, a small team of Australian researchers, funded partly by a grant from the Catholic Church, published a paper showing that olfactory stem cells can be induced to become heart cells, brain cells and nerve cells, without immune system rejection or formation of tumours.

The Lisbon study's authors concluded that their work showed that spinal cord injuries treated with cells derived from the patient's own body "is feasible, relatively safe, and potentially beneficial."

The olfactory mucosa as a source of stem cells is of interest to medical researchers because it is the only part of the body's nervous system capable of life-long regeneration that is readily accessible with minimal invasive techniques.

Dr. Alan Mackay-Sim, the lead researcher in the Australian study said that it is an under-examined field. "Whenever I presented a paper, the feedback I would get was that our work was 'interesting but weird'."

By Hilary White
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Re-Growing Nerves After Spinal Cord Injury

In a recent study, researchers from Johns Hopkins in Baltimore and the University of Michigan in Ann Arbor have uncovered a treatment involving the use of the enzyme sialidase to help regain growth of the spinal cord nerves after an injury.

Researchers mirrored a human injury in rats that would occur if the arm were forcefully tugged from the body, causing nerves to be jerked from the spinal cord, the arm to lose muscle and feeling, and the body to become unable to support the arm, such as in childbirth or a motorcycle accident. This was mimicked by severing nerves between the rats shoulder and spinal cord.

Rats were then given one of three enzymes into a transplanted nerve, put in to rejoin damaged nerve ends. Four weeks later, dyes were injected into the nerves to observe the growth of nerve fibers.
Sialidase, one of the enzymes given, proved to be effective, revealing more than twice the amount of new nerve fibers created by the dummy treatment of saline.

"Molecules in the environment of the injured spinal cord are specifically instructing the nerve not to re-grow," according to Ronald Schnaar, Ph.D., professor of pharmacology and neuroscience at Johns Hopkins. However, he adds researchers "have established that the enzyme sialidase, which destroys one of the molecules that inhibits nerve regeneration, is sufficient to robustly improve nerve fiber outgrowth from the spinal cord."

Surgical procedures to help nerve fiber growth are sometimes helpful, but researchers believe the addition of this treatment could be beneficial.

Dr. Schnaar and his colleagues at Johns Hopkins are testing sialidase to see if it can assist in other types of spinal cord injuries.
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Thursday, July 20, 2006

Study Establishes Safety of Spinal Cord Stem Cell Transplantation

Transplanting human embryonic stem cells does not cause harm and can be used as a therapeutic strategy for the treatment of acute spinal cord injury, according to a recent study by UC Irvine researchers.

UCI neurobiologist Hans Keirstead and colleagues at the Reeve-Irvine Research Center found that rats with either mild or severe spinal cord injuries that were transplanted with a treatment derived from human embryonic stem cells suffered no visible injury or ill effects as a result of the treatment itself. Furthermore, the study confirmed previous findings by Keirstead's lab - since replicated by four other laboratories around the world - that replacing a cell type lost after injury improves the outcome after spinal cord injury in rodents. The findings are published in the current issue of Regenerative Medicine, published by Future Medicine.

"Establishing the safety of implanted embryonic stem cells is crucial before we can move forward with testing these treatments in clinical trials," said Keirstead, an associate professor of anatomy and neurobiology and co-director of UCI's Stem Cell Research Center. "We must always remember that a human clinical trial is an experiment and, going into it, we need to assure ourselves as best as we can that the treatment will not cause harm. This study is an important step in that direction."

In 2005, Keirstead's lab was the first to coax human embryonic stem cells to become highly pure specialized cells known as oligodendrocytes. These cells are the building blocks of myelin, which acts as insulation for nerve fibers and is critical for maintenance of electrical conduction in the central nervous system. When myelin is stripped away through disease or injury, paralysis can occur.

In this study, as in the original one, when the rats suffering from severe spinal cord injury were injected with the oligodendrocytes seven days after injury, the cells migrated to the appropriate sites within the spinal cord and wrapped around the damaged neurons, forming new myelin tissue.

By contrast, the rats who were only mildly impaired showed no increase or decrease in myelin generation, and no change in their walking ability after transplantation. According to Keirstead, the injury was so minor that no loss of myelin occurred. Therefore, a treatment based on remyelination would have no effect and the animals recovered motor function on their own. More importantly, while the treatment did not help with functional recovery, it also did not impair it. Upon further examination, the scientists found no damage to the tissues surrounding the spinal cord indicating that the transplantation had not caused any damage to the animals.

"Our biggest safety concern was that in the case of a severe injury, any harm the stem cell-derived treatment could cause would be masked by the injury itself," Keirstead said. "In this study, we can see in animals that are only slightly injured that the transplantation does not cause visible harm and the injury is not hiding any damage the cells may have caused to the spinal cord or the surrounding tissue."

Keirstead is working with Geron Corp. to bring this treatment for acute spinal cord injury into Phase I clinical trials within the next year.
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Monday, July 17, 2006

Study Shows Spinal Cord Regeneration

A U.S. scientist has demonstrated in a lab animal the successful regeneration of injured spinal nerve endings and recovery of arm movements.

John Houle, professor of neurobiology and anatomy at Drexel University College of Medicine, demonstrated how a nerve removed from the animal`s leg and transplanted across a spinal cord injury -- in combination with enzyme digestion of scar material -- led to regeneration.

'This study represents a major milestone in the battle to return spinal cord injury patients to a state of mobility,' said Houle. 'However there is still a lot of work to be done to adapt this procedure to human use.'

He said a significant aspect of the study is the process applies to animals that are newly injured, as well as in animals with long-term injuries.

A second facet of the study is the ability of the specific enzyme, chondroitinase, to modify scar tissue, reducing its normal inhibitory nature and facilitating growth beyond the bridge.

The research project is detailed in the Journal of Neuroscience.
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Friday, July 14, 2006

BrainGate Trial Shows Promise for Motor Impaired

In a pilot trial of a device dubbed BrainGate, a man with paralysis of all four limbs could open simulated e-mail, play a game of Pong and adjust the volume on a TV using only his thoughts.

The findings could offer hope to people with severe motor impairments, said John P. Donoghue, a professor of neuroscience at Brown University and director of its Brain Science Program. Donoghue led development of the system and was the senior author of a report on it being published in today?s issue of the journal Nature.

The article is the first to provide in-depth scientific findings from the trial of BrainGate, a brain-to-movement system created and tested by Cyberkinetics Neurotechnology Systems Inc. of Foxborough, Mass. Cyberkinetics, the forerunner of Cyberkinetics Neurotechnology Systems Inc., was founded in 2001 under a licensing agreement with the Brown University Research Foundation. Brown faculty and students created the company based on research and technology developed in Donoghue's lab.

BrainGate consists of a surgically implanted sensor that records the activity of dozens of brain cells simultaneously. The system also decodes these signals in real time to control a computer or other external devices. In the future, BrainGate could control wheelchairs or prosthetic limbs. The long-term goal: pairing BrainGate with a muscle stimulator system, which would allow people with paralysis to move their limbs again.

The first trial patient, a 25-year-old man with spinal cord injury, used the device for nine months of the 12-month study period. The team also discusses the initial performance of a second trial patient, a 55-year-old man with spinal cord injury.

Based on the experience of these patients, the team found that movement signals persist in the primary motor cortex, the area of the brain responsible for movement, long after a spinal cord injury; that spiking from many neurons -- the language of the brain -- can be recorded and routed outside the human brain and decoded into command signals; and that paralyzed humans can directly and successfully control external devices, such as a computer cursor and robotic limb, using these neural command signals.

"We found that cortical activity can be modulated voluntarily even years after spinal cord injury," said Leigh Hochberg, MD, a Brown alumnus and lead author of the article. "Some researchers might have predicted that this part of the brain would alter its function dramatically after the spinal cord was injured. But that doesn?t seem to be the case. The movement-related signals are still there.

"What?s truly exciting is this: The cortical activity of a person with spinal cord injury, controlling a device simply by intending to move his own hand, is similar to the brain activity seen during preclinical studies of monkeys actually using their hands," Hochberg said. "Whether it is real or attempted movement, neurons seem to respond with similar firing patterns."
Hochberg is an investigator in neuroscience at Brown and a neurologist at Massachusetts General Hospital, Spaulding Rehabilitation Hospital and Brigham and Women?s Hospital. He is also an instructor at Harvard Medical School and an associate investigator with the Rehabilitation Research and Development Service at the Providence VA Medical Center.

Donoghue, senior author of the article and chief scientific officer at Cyberkinetics, said technical problems arose during the pilot trial, including signal decline after months of recording. However, the patients? control of the computer cursor and other devices was largely reliable. The first patient, for example, executed simple tasks such as moving a cursor to a target on a computer screen with 75 to 85 percent accuracy over many sessions. He also controlled a robotic arm, picking up pieces of hard candy and dropping them into a technician?s hand.

"What is also encouraging is the immediate response from the brain," Donoghue said. "When asked to 'think right' or 'think left,' patients were able to change their neural activity immediately. And their use of the device is seemingly easy. Patients can control the computer cursor and carry on a conversation at the same time, just as we can simultaneously talk and use our computers."

BrainGate is based on more than a decade of basic neuroscience research in the Donoghue lab, much of it funded by the National Institute of Neurological Disorders and Stroke, and much of it conducted by students. After proving the concept for BrainGate in experiments with monkeys, Donoghue and three Brown colleagues created Cyberkinetics to take their idea from bench to clinical trial.

Two of those founders -- Mijail Serruya, MD, a Brown Medical School graduate, and Gerhard Friehs, MD, a neurosurgery professor at Brown Medical School and director of functional neurosurgery at Rhode Island Hospital -- are co-authors of the Nature article. Jon Mukand, MD, clinical assistant professor of orthopaedics at Brown and principal investigator of one BrainGate trial site, also contributed. Maryam Saleh and Abraham Caplan, Cyberkinetics employees who worked directly with trial patients and are co-authors of the article, are Brown graduates.

At Brown, work on BrainGate continues through a collaboration with Cyberkinetics. Donoghue is working with Arto Nurmikko, professor of engineering, to develop a fully implantable, wireless microelectronic system to eliminate the need for external wires or bulky equipment. Michael Black, professor of computer science, is also working with the group to improve the neural decoding device so it can create control signals for complex motor tasks such as grasping.

Brown also has a collaborative research and licensing agreement with Cyberkinetics that allows eligible neuroscientists to access the company?s clinical trial data to conduct basic research.
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Wednesday, July 12, 2006

Surgery Offers Hope, but Price is High

Insurance won't cover operation that could restore function, feeling, normalcy to life.

A former Fort Campbell soldier who was deployed to Iraq in 2003 and 2004, Greg Minow is now a man on a different mission. Legs 4 Greg, his Web site, details the 28-year-old's quest to have an operation that may one day help him walk again.

On Nov. 6, 2004, Greg had a dirt bike accident that damaged his spinal cord, making him a T7 complete paraplegic. He and his wife, Alicia, 28, are determined to raise the $66,000 it will cost for Greg to have spinal cord decompression surgery and stem cell injection therapy. They are moving next month to California to be closer to the International Spinal Cord Regeneration Center in Tijuana, Mexico.

Injured people can qualify for the surgery if their spinal cord has not been completely severed and the dura sac surrounding the spinal cord is intact, allowing for flow of spinal fluid along the full length of the spinal cord. Greg meets both criteria, with approximately 30 percent of his neural fibers intact across the span of his spinal injury.

"When these two essential conditions are met, the healing program offered by the ISCRC is the most successful in the world today," says the center's Web site.

About the surgery
The surgery remodels the spinal canal, then uses injections of umbilical stem cells from the umbilical cords of babies to facilitate spinal regeneration.
"I found out about it through my oldest sister, who is an R.N.," Greg says.

His sister, Shelley Zastoupil, was working on a term paper and noticed a reference to the International Spinal Cord Regeneration Center in a friend's paper. Greg has since flown to Tijuana for extensive evaluation and found he is a good candidate for the surgery.

"The results are very encouraging," says the ISCRC Web site. "A number of our paraplegic patients are now walking. The quadriplegic patients treated to date are each making substantial progress. Patients in earlier stages of recovery are regaining sensation and control of bodily function."

Greg says even if the surgery doesn't allow him to walk again, he hopes to regain feeling in his torso.

"For him to get the smallest amount of function back, even to his bladder, would make a huge difference in his daily life," Alicia says.

"Being in a wheelchair isn't bad," Greg says. "It's the bowel and bladder that's bad."

Greg has to catheterize himself every three to four hours, and must wake up at 2 a.m. daily for as much as two hours of bowel care, using laxatives and stimulation to encourage elimination.
Regaining feeling in his lower torso could restore Greg to normal bowel and bladder function.

The price tag
After his surgery, Greg will have four hours per day of rehabilitation and repeated injections, at $8,000 each, of umbilical stem cells.

"I love working out, the physical, the rehab. I can handle the pain," Greg says. "The only obstacle facing us is the money."

Although he is leaving for California in a few weeks and hopes to have the surgery this fall, he cannot schedule it until he has half of the $66,000 as a down payment. He is trying to raise money through his Web site, as well as through sales of lollipops and chocolate bars at local Express Tan stores. Donations to date total $4,700.58.

When it was pointed out to him that if every person in Montgomery County donated 50 cents, his surgery would be paid for, a huge smile overtook Greg's face.

"Wouldn't that be cool?" he said.

By STACY SMITH SEGOVIA
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Paralyzed Mice Given Stem Cells Walk Again

Study suggests treatment may help repair damaged spinal cords.

Injections of human stem cells seem to directly repair some of the damage caused by spinal cord injury, according to research that helped partially paralyzed mice walk again.

The experiment, reported Monday, isn't the first to show that stem cells offer tantalizing hope for spinal cord injury ? other scientists have helped mice recover, too.

But the new work went an extra step, suggesting the connections that the stem cells form to help bridge the damaged spinal cord are key to recovery.

Surprisingly, they didn't just form new nerve cells. They also formed cells that create the biological insulation that nerve fibers need to communicate. A number of neurological diseases, such as multiple sclerosis, involve loss of that insulation, called myelin.

"The actual cells that we transplanted, the human cells, are the ones that are making myelin," explained lead researcher Aileen Anderson of the University of California, Irvine. "We're extremely excited about these cells."

The research is reported in Monday's issue of Proceedings of the National Academy of Sciences.

Stem cells are building blocks that turn into different types of tissue. Embryonic stem cells in particular have made headlines recently, as scientists attempt to harness them to regenerate damaged organs or other body parts. They're essentially a blank slate, able to turn into any tissue given the right biochemical instructions.

But they're not the only type of stem cell. Anderson and colleagues used fetal neural stem cells, a type that are slightly more developed than embryonic stem cells because they're destined to make cells for the central nervous system.

The researchers injured the spinal cords of mice and nine days later injected some with the human neural stem cells.

Four months later, the treated mice could again step normally with their hind paws. Mice given no treatment or an injection with an unrelated cell showed no improvement.

The question was what sparked that improvement. Injections of stem cells might simply stimulate the body to produce some healing factor, or they might directly repair damage themselves.

'Striking' improvements
So Anderson injected the animals with diphtheria toxin, which kills only human cells, not mouse cells. The improvements in walking disappeared, suggesting it was the cells themselves responsible for recovery.

"It was striking," Anderson said.
Finally, the researchers analyzed the actual mouse spinal cords to see what the human stem cells had turned into. The hope was that they would make neurons, or nerve cells, and some did.
But the bulk of the injected stem cells formed oligodendrocytes, a different type of cell that forms myelin, the insulation coating that is key for nerve fibers to transmit the electrical signals they use to communicate.

The toxin step was key to ensuring the transplanted cells themselves are functioning, and all researchers must provide such evidence because different types of stem cells almost certainly will work by different mechanisms in different tissues, said Dr. Doug Kerr, a Johns Hopkins University neurologist who is performing similar spinal cord research with embryonic stem cells.

Much more research must be done before testing stem cells in people with spinal cord injuries, cautioned Anderson. One question is how soon after an injury cells must be administered to have any effect - no one knows how nine days in a mouse's life correlates to the post-injury period for a person. Also, the mice were bred to avoid immune system destruction of the human cells, and suppressing a person's immune system because of similar transplant rejection risk poses big problems.

"The last thing we want to do is take someone who's living a productive life ? if confined, we all understand that ? and make them worse," said Anderson, who said the work also shows the need to study all types of stem cells. "The exciting part is the potential is there."

The research was funded by the nonprofit Christopher Reeve Foundation and the National Institutes of Health. StemCells Inc. of Palo Alto, Calif., provided the fetal-derived stem cells.
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Saturday, July 08, 2006

Swiss Make Breakthrough in Spinal Research

Novartis has begun clinical trials on humans with acute spinal injuries after Swiss scientists successfully re-grew nerve fibres in monkeys' damaged spinal cords.

It follows extensive research into spinal cord regeneration at the universities of Zurich and Fribourg, a report on which was published this week in Nature Medicine.

The scientists' findings, and the launch of the first trials in humans together represent an important step towards helping paraplegics rediscover their mobility.

"We have reached an important milestone in a very long process," Eric Rouiller, professor of physiology at Fribourg University told swissinfo.

In their six-year programme, researchers partially severed the spinal cords of 12 monkeys leading to paralysis in one hand.
The monkeys were then treated with an antibody ? known as anti-Nogo - that allowed nerves to re-grow up to 12 millimetres and enabled monkeys to regain 80 per cent of their movement.

Armed with these conclusions and encouraging pre-clinical findings, Novartis has now initiated the first phase of clinical trials in humans, in collaboration with the Spinal Cord Injury Centre at Zurich University and other European and American spinal injury centres.

The trials are designed for individuals who have suffered a serious accident in the ten days prior to treatment, rather than long-term paraplegics.

The initial feasibility phase involves installing a small pump in about 15 patients to inject the anti-Nogo antibody into the spinal column.

Novartis says that if all goes well, the next stage should start in spring 2007, investigating the safety and the effectiveness of this therapeutic approach on around 100 patients.

Caution
Despite their general optimism, researchers remain cautious about the success of the trials.

Rouiller stresses their long-term aspect and is keen that patients' hopes are not raised unduly.

"You have to remember that clinical trials are the most difficult stage and can reserve some unpleasant surprises," he added.

Martin Schwab, chairman of Zurich's Neuroscience Centre and a leading Swiss neurobiologist, compares a spinal injury to a bomb going off in a computer room.

"It is not surprising, therefore, if new nerve connections do not grow back correctly," he says.

In a spinal accident, crushed spinal column injuries are more common than severed nerved endings.

But Rouiller is convinced that his monkey tests are extremely representative of situations where the spinal column is not totally destroyed.

Experimentally, researchers are now suggesting that a better outcome is possible for people with spinal cord injuries.

The realistic hope, according to Schwab, is that paraplegic patients will get some movement back ? probably with crutches or handrails ? as well as restored bladder control.

Scientists believe that regaining mobility involves a multi-therapy approach, involving a Nogo blocker, an agent to boost nerve growth, and some kind of cell transplant for treatment of severe paralysis.

Whatever happens, Schwab is delighted to see a proliferation of research projects into paralysis treatment: "Even if our approach doesn't lead to a therapy, another will follow close on its heels."
swissinfo, Simon Bradley

CONTEXT
In 1988, Martin Schwab first identified a substance in the central nervous system that prevents the brain and spinal cord from repairing themselves after an injury.
Dubbed Nogo because of its inhibiting effect, the gene produces a protein, which prevents damaged nerves from re-growing after they are cut.

His team developed an antibody that neutralises the blocking protein and allows the nerves to reconnect.

Researchers carried out the first tests on rats, which were paralysed by having their spinal cords partially cut; they were then given the antibody. The nerves re-grew and the animals resumed normal activities.

Eric Rouiller and his team continued tests on 12 macaque monkeys, which have similar corticospinal tracts to humans.

After their spinal cords had been partially cut and treated with the antibody, the partially paralysed animals regained 80 per cent of their hand movements.

KEY FACTS

* In Switzerland 2,200 people have spinal cord injuries.
* About 180 new paraplegics are registered every year, 50% with severe injuries.
* The two most common areas of the spinal cord most injured are the cervical spine and the lumbar spine.

By: Simon Bradley
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Wednesday, July 05, 2006

A Cure 'Will Come' for Paralysing Spinal Injuries

An American spinal injury expert has been updating Bermuda medics on the latest developments in the care and rehabilitation of patients who have suffered debilitating injuries to their spines.

Dr. Kevin O'Connor, medical director of the spinal cord injury programme at Boston's Spaulding Rehabilitation Hospital, also met with health insurance professionals on the Island.

A handful of patients from Bermuda end up at the Boston hospital each year to receive specialist treatment.

Care for spinal injuries is a highly specialised area of medicine and is continuously under review as efforts are made to find a cure for one of the most debilitating medical conditions.

The late Superman actor Christopher Reeve was one of the most high-profile sufferers of a spinal cord injury. After being thrown from a horse he was riding in 1995 he was left unable to move his body from the neck down.

Mr. Reeve remained hopeful that stem cell research would one day succeed in finding a way to restore the ability of movement in those who had suffered a spinal cord injury.

"There is no cure for spinal cord injury at the moment. But whether one comes through stem cell research, or another method, a cure will come. It is a matter of time," said Dr. O'Connor.

In the meanwhile the role of the spinal cord injury medical professionals is to find ways of keeping patients healthy and in good shape.

"We try to have people with these injuries come to our hospital as soon as possible," said Dr. O'Connor.

Getting patients to the specialist unit at Spaulding is important to avoid complications setting in such as bed sores and infections. As patient treatment progresses, the future needs of the injured person are assessed.

During his visit to Bermuda, Dr. O'Connor noted the hilly topography of the Island, an important factor to consider when working out what abilities and mobility assistance a Bermudian patient will require when they return to the Island.

The Boston hospital treats around five or six patients from Bermuda each year.

While on the Island, Dr. O'Connor met with health insurance companies that have previously sent spinal injury patients to Spaulding to inform them of the hospital's programme and the latest research, and also spoke with health professionals at King Edward Memorial VII Hospital on "research, finding a cure for spinal cord injury, interventions and updates".

He said: "The number one cause of spinal injuries in the USA is falls, but road accidents and diving accidents account for a large percentage of such injuries in Bermuda.

"Some people will not make a full recovery. What we try to do is make people as independent as possible.

"The hardest thing is adjusting to the injury. I see several hundred people with spinal cord injuries each year. Imagine what it is like not not be able to feel your sock or shoe or even your leg. So many things require an intact spinal cord."

Dr. O'Connor said: "We teach patients about themselves and how to adjust to the changes in their lives."

By Scott Neil
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