Tuesday, October 26, 2004

New Ways to Reverse Paralysis

Each year, more than 11,000 people will become paralyzed in the United States. It happens in a split second, but it changes lives forever.

Researchers are constantly looking for ways to reverse the condition. Now there is a promising discovery that could put them on the fast track.

Neuroscientist Mary Bartlett Bunge has found her passion at the Miami Project to cure paralysis. "These are the most exciting findings that I have seen in my laboratory in my 15 years on the Miami Project."

In a three-year study, Bunge restored walking ability in paralyzed rats to up to 70 percent normal function. "To see something for the first time is a creative and thrilling experience."

The therapy combines three treatments believed to help paralysis. One of those treatments is schwann cells. "Schwann cells enable regeneration of neuro-fibers in the peripheral nervous system that is in your legs and arms."

Cyclic AMP is also used. It's injected into the spinal cord to improve the growth of neuro-fibers. And the antidepressant rolipram is used to maintain the AMP at high levels.

"This finding opens up new possibilities for treating humans with spinal cord injury," Dr. Bunge said.

Dan Castellanos was paralyzed more than 20 years ago. He's now a researcher himself at the Miami Project and calls Bunge's research a breakthrough. "I think it is revolutionary and it comes at a really important time."

He's excited about the implications. "I think it shows great potential and I think it is a good time to be here and it is a good time to be watching."

You can bet both scientists and patients are going to be watching and waiting.

Bunge said the combination showed the most benefit, but the antidepressant rolipram was also effective when used alone.

She said there are still many questions that need to be answered before this combination can be tested in humans.

By: Ivanhoe Newswire
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Nerve Navigation Findings Prompt New Direction for Spinal Cord Research

A piece of the puzzle of how nerves find their way across the midline of the brain and spinal cord in a developing embryo has been found by Medical College of Georgia researchers.

They have found that an enzyme called focal adhesion kinase tells the arm-like extension of a neuron to cross the midline of the spinal cord, says Dr. Wen-Cheng Xiong, developmental neurobiologist and lead author on the paper in the November issue of Nature Neuroscience. After crossing, the axon becomes part of the complex network that enables the right side of the brain to control the left side of the body and vice versa.

The finding helps explain normal development of the nervous systems and provides a new target in the search for ways to re-establish connections -- and the movement and feeling they enable -- lost to spinal cord injuries. "This kinase plays a role in helping direct axon movement across the spinal cord during development," Dr. Xiong says. "How it does that is one of the questions we hope to answer next. We still have a lot of questions." Among those is why this mechanism doesn't seem to work after development is complete. "If the spinal cord is injured, why doesn't it re-cross that boundary?" she says. "Why are these molecules not functioning well in the adult?"

Focal adhesion kinase already is a hot topic among scientists studying how cells migrate and how tumor cells spread. Now, Dr. Xiong and her collaborators have found the enzyme also plays an important role in central nervous system development. She explains that for axons to journey across the spinal cord, floor plate cells along this natural midline of the developing body secrete a guidance or cue factor called netrin-1. "If this molecule is deleted, this axon cannot cross. It just stays on this side" and the developing embryo will die, a testimony to netrin?s expansive role in getting cells where they need to be. "This factor plays a critical role for nearly all the neurons to cross the midline, even in the cortex or hippocampus of the brain," Dr. Xiong says.

A receptor on the axon called DCC, or Deleted in Colon Cancer, responds to the signal from netrin. But why the axon knows to move in a certain direction once it sees that signal was an unknown, Dr. Xiong says. The researchers have now found that once this receptor binds to netrin, focal adhesion kinase is activated that tells the axon to reorganize its structure or cytoskeleton and the restructured axon knows how to move. When they delete the kinase, the axon doesn't make the proper journey or the proper connection.

Developing axons can sense and navigate their environment but how the two functions work together to result in the axon getting where it needs to be is poorly understood, Dr. Xiong says. "Everybody in the developmental neurobiology field is wondering what is the mechanism, how the neuron, once it senses the environment, couples with the motor activity. This provides information for that kind of puzzle," she says of the newly published work.

The researchers are looking for other molecules that also play a role in directing axonal growth. "We have lots of information about how this molecule talks with other molecules," Dr. Xiong says. "We just need to get a system to figure out how they talk to each other." She's also moving toward an injury model to see what happens to this molecular talk after a spinal cord injury. "We know this factor can turn on but we don't know how it turns on. If you sever the spinal cord, the important crossing of the axon is gone. Right now, we don't know how to make it go back."

Drs. Xiong's MCG collaborators on the study include her husband, Dr. Lin Mei, also a developmental neurobiologist; research technician Zhu Feng and graduate student Qiang Wang as well as researchers at the University of Alabama at Birmingham; Johns Hopkins University School of Medicine; and Washington University School of Medicine.

Her research is funded by the National Institutes of Health.
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Monday, October 11, 2004

Christopher Reeve, an advocate for spinal cord research, dies at age 52

'Superman' star Christopher Reeve, an advocate for spinal cord research, dies at age 52

Monday, October 11, 2004

MOUNT KISCO, N.Y. - "Superman" actor Christopher Reeve, who turned personal tragedy into a public crusade and from his wheelchair became the nation's most recognizable spokesman for spinal cord research, has died. He was 52.

Reeve went into cardiac arrest Saturday while at his Pound Ridge home, then fell into a coma and died Sunday at a hospital surrounded by his family, his publicist said,

His advocacy for stem cell research helped it emerge as a major campaign issue between President Bush and Sen. John Kerry. His name was even mentioned by Kerry during the second presidential debate on Friday.

In the last week Reeve had developed a serious systemic infection from a bed sore, a common complication for people living with paralysis. He entered the hospital Saturday.

Dana Reeve thanked her husband's personal staff of nurses and aides, "as well as the millions of fans from around the world."

"He put up with a lot," his mother, Barbara Johnson, told the syndicated television show "The Insider." "I'm glad that he is free of all those tubes."

Before the 1995 horse-riding accident that caused his paralysis, Reeve's athletic, 6-foot-4-inch frame and love of adventure made him a natural choice for the title role in the first "Superman" movie in 1978. He insisted on performing his own stunts.

"Look, I've flown, I've become evil, loved, stopped and turned the world backward, I've faced my peers, I've befriended children and small animals and I've rescued cats from trees," Reeve told the Los Angeles Times in 1983, just before the release of the third "Superman" movie. "What else is there left for Superman to do that hasn't been done?"

Though he owed his fame to it, Reeve made a concerted effort to, as he often put it, "escape the cape." He played an embittered, crippled Vietnam veteran in the 1980 Broadway play "Fifth of July," a lovestruck time-traveler in the 1980 movie "Somewhere in Time," and an aspiring playwright in the 1982 suspense thriller "Deathtrap."

More recent films included John Carpenter's "Village of the Damned," and the HBO movies "Above Suspicion" and "In the Gloaming," which he directed. Among his other film credits are "The Remains of the Day," "The Aviator," and "Morning Glory."

Reeve's life changed completely after he broke his neck in May 1995 when he was thrown from his horse during an equestrian competition in Culpeper, Va.

Enduring months of therapy to allow him to breathe for longer and longer periods without a respirator, Reeve emerged to lobby Congress for better insurance protection against catastrophic injury. He moved an Academy Award audience to tears with a call for more films about social issues.

"Hollywood needs to do more," he said in the 1996 Oscar awards appearance. "Let's continue to take risks. Let's tackle the issues. In many ways our film community can do it better than anyone else."

He returned to directing, and even returned to acting in a 1998 production of "Rear Window," a modern update of the Hitchcock thriller about a man in a wheelchair who is convinced a neighbor has been murdered. Reeve won a Screen Actors Guild award for best actor in a TV movie or miniseries.

"I was worried that only acting with my voice and my face, I might not be able to communicate effectively enough to tell the story," Reeve said. "But I was surprised to find that if I really concentrated, and just let the thoughts happen, that they would read on my face."

Reeve also made several guest appearances on the WB series "Smallville" as Dr. Swann, a scientist who gave the teenage Clark Kent insight into his future as Superman.

In 2000, Reeve was able to move his index finger, and a specialized workout regimen made his legs and arms stronger. With rigorous therapy, involving repeated electrical stimulation of the muscles, he also regained sensation in other parts of his body. He vowed to walk again.

"I refuse to allow a disability to determine how I live my life. I don't mean to be reckless, but setting a goal that seems a bit daunting actually is very helpful toward recovery," Reeve said.

Dr. John McDonald treated Reeve as director of the Spinal Cord Injury Program at Washington University in St. Louis. He called Reeve "one of the most intense individuals I've ever met in my life."

"Before him there was really no hope," McDonald said. "If you had a spinal cord injury like his there was not much that could be done, but he's changed all that. He's demonstrated that there is hope and that there are things that can be done."

Dr. Raymond Onders, who implanted electrodes in Reeve's diaphragm in a groundbreaking surgery to help him breathe, said the sore that led to the infection was not Reeve's only recent health problem.

"Many different problems develop after nine years of being dependent on a ventilator, not being able to move yourself, having intestinal problems. ... It just slowly builds up over the years," Onders told ABC News' "Good Morning America."

Reeve was born Sept. 25, 1952, in New York City, son of a novelist and a newspaper reporter. About the age of 10, he made his first stage appearance - in Gilbert and Sullivan's "The Yeoman of the Guard" at a theater in Princeton, N.J.

After graduating from Cornell University in 1974, he landed a part as coldhearted bigamist Ben Harper on the soap opera "Love of Life." He also performed frequently on stage, winning his first Broadway role as the grandson of Katharine Hepburn's character in "A Matter of Gravity."

Reeve's first movie role was a minor one in the submarine disaster movie "Gray Lady Down," released in 1978. "Superman" soon followed. Reeve was selected for the role from among about 200 aspirants.

While filming "Superman" in London, Reeve met modeling agency co-founder Gae Exton, and the two began a relationship that lasted several years. They had a son and a daughter, but never wed.

Reeve later married Dana Morosini; they had one son, Will, 12. Reeve also is survived by his mother, Barbara Johnson; his father, Franklin Reeve; his brother, Benjamin Reeve; and the children from his relationship with Exton, Matthew, 25, and Alexandra, 21.

Funeral plans were not immediately announced.

In his 1998 book, "Still Me," he recalled that after the accident, when he contemplating giving up, his wife told him: "I want you to know that I'll be with you for the long haul, no matter what. You're still you. And I love you."

His children helped, too, he told interviewer Barbara Walters.

"I could see how much they needed me and wanted me ... and how lucky we all are and that my brain is on straight."
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Thursday, October 07, 2004

Spinal Cord Repair Trials Given Go-Ahead

Human trials of a technique with the potential to repair spinal cord injuries are set to start within three years, experts said today.

The work, which could help thousands of disabled people regain movement, will be carried out at University College London's new Spinal Repair Unit.

The plans were outlined today as UCL launched a £300 million fundraising campaign to boost work across the university.

Professor Geoff Raisman and his team from the National Institute for Medical Research (NIMR) will join the Spinal Repair Unit to start work towards human trials.

They have already demonstrated that it is possible for severed spinal cord nerve fibres to grow back and restore lost functions.

Prof Raisman discovered that there was one part of the nervous system ? a region in the nasal cavity involved in the sense of smell - in which nerve fibres were in a state of continuous growth during adult life.

The researchers transplanted cells from this region into the injured spinal cord of rats and found they were able to integrate into the damaged pathways and lay a "bridge" over the gap in the nerve fibres caused by injury.

The team believe the technique could be transferred to humans, who would act as their own cell donors.

They hope to start clinical trials in humans in the next two to three years.

Prof Raisman, who will be the first director of the unit, said: "I have spent my research career in trying to find a treatment for spinal cord injury, and I never anticipated that we would get this far when I started out."

"We have been able to persuade the medical profession that a cure was possible, and the fact that we have now joined UCL, and will be able to collaborate with the UK's major neurosurgical team to develop human trials, represents a major step forward."

It is estimated that 40,000 people in the UK are living with a spinal cord injury, with varying degrees of disability.

"It goes without saying that we do not wish to raise false hopes in patients who are living with spinal cord injury," Prof Raisman added.

"However, our work to date has indicated that, contrary to what was previously thought, the spinal cord does have the potential to repair itself.

"That is why the UCL Institute of Neurology believes that human trials are a logical next step."

The work is being supported by the British Neurological Research Trust and other spinal research charities.

Roger Lemon, director of UCL?s Institute of Neurology, said: "Geoff Raisman and his team have shown that the repair of the injured spinal cord is now a real possibility."

"However, in order to translate the very exciting findings in the rat into benefits for patients, it is essential to have the scientists and clinicians working together, and this move means that we can now start preparing for the day when the first trials will begin."

UCL also unveiled plans today to create the world's first Functional Electrical Stimulation (FES) Sports Centre.

The centre would help paraplegics buy adapted tricycles with FES equipment to let them cycle using their leg muscles.

The system works by stimulating paralysed muscles by passing short pulses of current through electrodes on the skin which moves the legs.

The rider has a "throttle" to control how much stimulation is applied.

Professor Nick Donaldson wanted to create the centre as a support service to help people take advantage of the FES equipment as it became increasingly available.

Tricycles will cost up to £3,000 and stimulators £1,000, but staff at the centre can give advice on how patients can apply to charities for assistance.

Those visiting the centre will also help researchers fine-tune and improve the technology.

Prof Donaldson, of UCL's Implanted Devices Group, said: "Many people with a disabling spinal injury could make use of FES, but at present it remains primarily a research tool, used in a handful of labs such as ours, so the only people who use it are those taking part in studies."

"We want to offer a public FES service through this pilot centre and we hope other centres will spring up."

By: Lyndsay Moss, Health Correspondent, PA News
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Kerry shows support of stem cell research

Presidential nominee Sen. John Kerry and actor-turned-activist Michael J. Fox discussed the issue of stem cell research with an enthusiastic crowd Monday morning at Winnacunnet High School in Hampton, N.H.

In August of 2001 President Bush announced that the federal government would only support restricted study of stem cells. This allowed for 60 stem cell lines to be researched, many of which Kerry and Fox said are either useless or tainted. Advocates of stem cell research believe that conditions such as Parkinson's, Alzheimer's, heart disease and spinal cord injury, among others, could be aided or cured through stem cell therapy.

Kerry, who promised at least $100 million dollars of federal funding a year toward stem cell research, said, "President Bush just doesn't get it. Faced with the facts, he just turns away. Time and time again, he's proven that he's stubborn, out of touch, and unwilling to change."

Michael J. Fox, who suffers from Parkinson's, said that President Bush, "gave us a car with no gas and then congratulated himself for giving us the car. Instead of leading the world with our research, we're following it."

Over 100 million Americans and over 600,000 New Hampshire residents who suffer from a variety of diseases could potentially benefit from stem cell research, according to the Kerry campaign.

One of those 600,000 is the son of Steve Walter, of Londonderry. Walter voted for President Bush in 2000 but his seven-year-old son Alex has made him a Kerry supporter. Alex has type I diabetes and endures over 12 needle pricks and five insulin shots a day. Walter believes stem cell therapy could help his son Alex, who has developed scar tissue under his stomach and triceps and is susceptible to blindness, nerve damage and stroke, all of which are side effects of diabetes. Walter said, "President Bush is being morally irresponsible [and is showing] total disregard for human life."

According to a Harris Interactive Poll taken in August, 73 percent of Americans support stem cell research.

Kerry bolstered his stance by citing backing by Nobel Prize winners, scientists and many U.S. senators, including Republican John McCain. Kerry told the crowd that America has always been known for searching and finding medical breakthroughs yet, "now we stand at the edge of the next great frontier-but instead of leading the way, we're stuck on the sidelines. This president is making the wrong choice to sacrifice science for extreme right-wing ideology."
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Better Recovery for Spinal Cord Injuries

Patients with spinal cord injuries could benefit from early magnetic resonance imaging, according to the findings of a new study.

Canadian neuroscientists discovered that MRI technology could determine if performing surgery would benefit patients. They found trauma-induced spinal cord compression on MRIs predict a poorer neurological recovery.

Surgery can relieve spinal cord compression. However, unless surgeons are fairly certain the procedure will benefit the patient, they are generally reluctant to operate because of the risks. Researchers say this study should remove that uncertainty.

Researchers evaluated the records of 22 patients who were admitted to the hospital with spinal cord injury and who were assessed with both MRI and computed tomography at admission and at a follow-up examination about 10 months later. They examined whether there is an association between the degree of spinal cord injury compression in the period just after traumatic injury and clinical neurological outcome. They found evidence of spinal cord compression on MRI, but not CT, predicted a poorer recovery.

Researchers conclude, "It is our view MRI should be done whenever feasible in all patients with an acute spinal cord injury to evaluate the extent of spinal cord compression. It is our practice to undertake urgent and thorough decompression of the spinal cord with the view of trying to maximize the extent of neurological recovery."

This article was reported by Ivanhoe.com, who offers Medical Alerts by e-mail every day of the week. To subscribe, go to: http://www.ivanhoe.com/newsalert/.

SOURCE: Presented at the 129th annual meeting of the American Neurological Association in Toronto, Oct. 4, 2004
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