April 09, 2005
Tommy Lee Jones And John Walsh Join Forces
John Walsh, who turned his personal tragedy into a national movement through his highly acclaimed “America’s Most Wanted” television program, joins Tommy Lee Jones, who won an Oscar for chasing America’s Most Wanted in the movie The Fugitive, to play in a unique Safari Adventure Gala and Celebrity Polo Match on Saturday, April 9 at the International Polo Club Palm Beach.
They will be joined by Mathias Guerrand Hermes, John Goodman and 10-goalers Adam Snow and Mike Azarro in a two-chukker exhibition match as part of the inaugural Safari Adventure Gala, a unique fundraiser to benefit of the Buoniconti Fund to Cure Paralysis, a charity founded by NFL Hall-of-Famer Nick Buoniconti.
The Buoniconti Fund to Cure Paralysis is the national fundraising arm of the Miami Project, the world’s largest, most comprehensive research center dedicated to finding more effective treatments and, ultimately, a cure for paralysis that results from spinal cord injury.
The two-chukker exhibition will be followed by a journey through an exotic jungle and spectacular interactive cooking displays and dinner created by celebrities and local chefs and enjoyed in the relaxed comfort of a safari hideaway.
Following the polo match, several hundred guests will enjoy sumptuous cuisine individually prepared by chefs from some of the area’s favorite restaurants.
“The international polo community brings a great deal of beauty, art and exciting sport into the world at a great peril to life and limb,” Jones said. “Many of our friends are crippled. It is a natural partnership with the Miami Project to seek a cure for what has been thought of as terminal spinal cord injury. With the development of stem cell research, we all want take the word terminal out of equation.”
For more info., or to order tickets, call Stephanie Sayfie Aagaard at (305) 243-4656 or e-mail saagaard@miami.edu.
http://www.thecrier.com/default.asp?
April 06, 2005
Beijing offers beginning in quest to walk again
By ALAN BAVLEY - The Kansas City Star
David Landewee already can feel sensations in his stomach. His breathing is stronger. He can even sit up and flex muscles in his legs.
Nearly 10 years after a car wreck left him paralyzed from the chest down, the 42-year-old Clay County man now is confident he'll walk again.
Landewee gained this new optimism after traveling to China in February for a $20,000 operation to inject cells from aborted fetuses into his spine.
“I've already got way more than my money's worth, and the real results haven't begun yet,” Landewee said.
The procedure has drawn hundreds of paralyzed patients from the United States and other countries who hope these cells will stimulate their damaged spinal cords to regenerate. Patients with ALS also have gone to have fetal cells injected into their brains to halt the progression of their illness.
The Beijing hospital where American-educated neurosurgeon Huang Hongyun offers these procedures now has a waiting list that extends for years.
But many scientists are advising caution. It's true, as Landewee has found, that patients often gain immediate but fairly small benefits from the operation. But Huang has not offered evidence that they continue to make the kind of progress he has told Landewee to expect.
The Miami Project to Cure Paralysis, a research center at the University of Miami, has pointedly withheld its endorsement of Huang's surgery and warned patients that they could be disqualified from tests of more promising treatments in the future if they undergo the procedure.
Even researchers who are supportive of Huang's work are guarded in their opinions.
“It's not a cure. It's not a miraculous treatment, but this is a first step,” said Wise Young, a Rutgers University neuroscientist who helped train Huang and who has visited him in China and seen his work. “It appears to be producing modest improvements in some people. For many patients this is the first therapy that works.”
The spinal cord is a bundle of nerves that transmits sensations from the body to the brain and relays orders from the brain to the muscles that move the body.
Spinal cord injuries had long been considered permanent because the nerve cells in the cord do not grow back effectively. But in recent years, promising research into regenerating the damaged nerves has given new hope to the estimated 247,000 people in the United States with spinal cord injuries. Researchers are using stem cells, nervous system cells and experimental drugs to coax the nerves to grow.
The late Christopher Reeve, the actor who was paralyzed in a horse riding accident in 1995, made improved treatment of spinal cord injuries a high-profile issue and expressed hope he would walk again.
Reeve staunchly supported controversial research on stem cells to regenerate spinal cord nerves. Huang, however, has taken a different but equally contentious approach.
Instead of stem cells, his therapy employs specialized fetal cells that are involved in the sense of smell. The olfactory nerve, which sends sensations of smell to the brain, continually regenerates throughout a person's life. The cells Huang uses, called olfactory ensheathing glial cells, support this regeneration by wrapping around nerve fibers and promoting their growth.
After Landewee was injured, he kept himself in physical shape, confident that a cure for his injury would be available someday. He has worked out regularly on an exercise bicycle with electrodes that stimulate his thigh muscles. He's used other machinery to keep his leg muscles stretched and limber.
Now, he is undergoing physical therapy to try to build on the improvements from the operation.
In September 1995, Landewee was on his way to his job as an electrician at the Ford Claycomo plant when he swerved to avoid a car entering the highway and his car rolled.
Several weeks later, he woke in a hospital bed. His spinal cord was nearly severed; only a few connecting strands remained at the point of the injury. He was told he would never walk again.
Like Reeve, Landewee became an advocate, helping pass a Missouri law to use some of the revenue from traffic violations for spinal cord research. He also began his search for an effective treatment.
“There's a lot of things out there, but it's like snake oil — they're trying to take your money,” Landewee said.
Last year, when Huang's work began to receive positive publicity, Landewee signed up for the surgery, paying for it out of pocket.
He and his father, Irvin, arrived in Beijing on Feb. 25. After eight days of X-rays, blood work and other medical tests, Landewee underwent the surgery.
Huang made small cuts into his backbone above and below the injured area of his spinal cord. Through those incisions, Huang injected the fetal cells.
About five or six days after surgery, Landewee noticed muscle movement in his legs.
“It takes a lot of focus,” he said. “You're trying to use them after nine and a half years. But I can get them to tense up.”
While he recuperated, Landewee became somewhat of a celebrity at the hospital. He was interviewed by television crews from Turkey, Australia and several other countries who were there to cover Huang's work.
Landewee also saw other patients at the hospital improve as well — spinal cord injury patients who also were able to move parts of their bodies. ALS patients regained dexterity in their hands and walked with assistance.
Huang has not offered much of an explanation for what is happening to his patients.
“It's very hard to explain. It's too fast, too quick (for nerve regeneration),” Huang told a Knight Ridder reporter in Beijing last year. “There is some mechanism. … I don't know why it works. (But) it helps patients.”
Young, of Rutgers, said he has used laboratory rats to successfully duplicate Huang's surgery. Just like the human patients, the animals quickly regained limited sensation and movement, he said.
What the fetal cells may do, Young theorized, is stimulate the surviving nerve fibers to sprout new connections.
“Those (connections) could happen in a few days,” he said.
A half-dozen other research groups also have reported positive results using olfactory cells to treat spinal cord injuries in animals, Young said.
“This is not fly-by-night therapy,” he said. “It has a strong scientific basis.”
But much of the U.S. medical community remains skeptical about Huang's results, particularly any claims of long-term benefits.
“He believes he's giving a cure to people,” said Maura Hofstadter of the Reeve-Irvine Research Center at the University of California-Irvine. “But he doesn't follow his patients. They go there. They have the surgery. They're monitored for two weeks and sent on their way. We don't know what happens to them after that.”
Although the fetal cell injections may be stimulating nerves to make new connections, Hofstadter said, well-motivated patients also may be benefiting from the placebo effect by trying to do things they otherwise wouldn't attempt.
Greg Cash of the ALS Association expressed similar doubts.
“We have more questions than we have answers about what he's doing,” Cash said. “His methods aren't being shared with the world, and there's no follow-up to see if it's doing anything.”
But Young thinks there's enough evidence of benefits from Huang's surgery to justify a well-controlled study that follows patients over time. Such a study in the United States would require approval of the Food and Drug Administration. But Young plans to help Huang set up a program next year for long-term monitoring of his patients in China.
For now, Landewee and his family have to believe.
“I heard Doctor Huang tell Dave, ‘You will walk.' I heard it from his own mouth. I'm from Missouri and I want to be shown, but I hope it's true,” Irvin Landewee said.
To reach Alan Bavley, call (816) 234-4858 or send e-mail to abavley@kcstar.com.
http://www.kansascity.com/mld/kansascity/news/local/11319850.htm?template=contentModules/printstory.jsp
© 2005 Kansas City Star and wire service sources. All Rights Reserved.
http://www.kansascity.com
HEALING THERAPIES NEWSLETTER
Believing that the development of new therapies for spinal cord injury (SCI) requires global and multidisciplinary cooperation, organizers invited scientists with diverse viewpoints from throughout the world. As in the previous symposium, a highlight was the participation of Dr. Rita Levi-Montalcini, the 1986 Nobel Laureate in Medicine for discovering nerve growth factor over 50 years ago. Following are summaries of a few presentations:
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NUEROMONITORING:
A keynote lecture was given by Dr. Milan Dimitrijevic (Texas), an internationally recognized neurophysiologist whose investigations on spinal-cord conduction have greatly contributed to our understanding of SCI. He noted that the spinal cord is much more physiologically complex than originally thought; however, rather than making functional repair more challenging, this complexity generates opportunities for new rehabilitation strategies.
Dimitrijevic discussed how various interventions after acute SCI - such as surgical stabilization and reconstructions - could be monitored by recording conduction above and below the injury site. By using such neuromonitoring, a surgeon can have valuable information on where spinal-cord integrity is being preserved.
Through knowledge gained from such monitoring, it may be possible to initiate physiological-like electrical stimulation of the non-injured conducting axons to prevent effects of disuse and secondary lesions.
In chronic injuries, neuromonitoring could assess the efficacy of various function-restoring interventions. For example, the neuromonitoring of bridging tissue transplants could provide information about whether the transplants are filling the gap, integrating with surviving tissue, decreasing scar tissue, reducing cavity formation, staying where placed, and increasing migration of blood vessels or cells that facilitate axonal regeneration.
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REROUTED NERVES:
Brunelli, the symposium organizer, reviewed his research on surgically rerouting human peripheral nerves (i.e., those outside of the spinal cord and brain) around the injury site to reestablish functional neuronal connections. For example, he has restored some function by redirecting the wrist's ulnar nerve and connecting it to nerves that control leg functioning below the injury site. After this procedure, a patient with a complete spinal-cord transection could stand up and walk short distances.
In another procedure carried out in a woman with a complete thoracic transection, the peroneal nerve (to the leg) was used as a bridge directly from the spinal cord above the injury site to the nerves of the gluteus and quadriceps muscles. After two years, she was able to walk 30-40 meters with a walker.
Because the second procedure represents a direct peripheral-nerve-to-spinal-cord connection, it challenged traditional beliefs on how neurons control muscle function. Specifically, in the previous symposium, Levi-Montalcini was troubled by the implications of Brunelli's work because upper motor neurons (nerves within the spinal cord) and lower motor neurons (nerves that leave the cord to connect to muscles) use different neurotransmitters (chemicals released from a neuron ending that interacts with an adjacent neuron or muscle cell). Hence, theoretically, the muscle should not be triggered due to neurotransmitter incompatibility.
Because scientists pay special attention to the suggestions of Nobel laureates, Brunelli and collaborators have since shown that this procedure indeed restores function in rats in spite of this putative incompatibility. Specifically, they have demonstrated that the target muscles are genetically reprogrammed, producing receptors that are responsive to the neurotransmitters released by the upper motor neurons that have grown to the muscles through the peripheral nerve bridge.
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RADIATION:
Dr. Nurit Kalderon (New York) has treated acutely injured rats with radiation, which destroys nascent scar-tissue that blocks neuronal regeneration. Although the spinal cord attempts to repair itself soon after injury, the decay process takes over after the third week. However, when x-rays were directed to the transected spinal cord during the third week, the cord continued to repair. Once the wound was healed, severed neurons grew across the site, restoring some function. Because x-rays destroy obstructive cells, spinal-cord repair can continue.
Kalderon carried out additional studies in rats injured by contusion, which more closely resembles most human injuries. Before radiation, surgery was performed to reduce secondary damage caused by swelling and fluid buildup. Starting 12 days postinjury, the lesion was radiated daily for 10 days at a level proportionate to that clinically used to remove human cancer. Analysis indicated significant tissue repair.
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ACTIVITY-MEDIATED NEUROREHABILITATION:
Dr. Humberto Cerrel Bazo (Italy) discussed the use of activity-mediated training - such as functional electrical stimulation (FES) - to maximize function after SCI. His talk, as well as others, referred to the spinal cord's "central pattern generator," which can sustain lower-limb repetitive movement, such as walking, independent of direct brain control.
Cerrel Bazo noted that we are learning much more about 1) the plasticity (adaptive mechanisms by which the nervous system restores itself) of the sensorimotor nervous system above and below the injury site (i.e., brain-spinal-cord-motor unit), and 2) the residual activity of muscles, bladder, bowel, etc. amenable for enhanced function through new circuitry or artificial means.
He reviewed how a sacral-sparing assessment procedure (gauges anal sensation and control) within 30-days of injury is useful for predicting future functional recovery.
Through FES training, Cerrel Bazo has shown promising, plasticity-associated outcomes, which, in turn, suggests intriguing possibilities about the integration of different systems above and below the injury site. FES may enhance residual potential in people with chronic SCI by generating a movement pattern useful for standing, stepping, and cycling.
However, if residual activity remains dormant over the long term, awareness to support activity may be lost. A properly stimulated sensorimotor nervous system may generate activity useful for the functional integration of different systems. In this sense, FES, the awareness-learning process, and training mediated-activities may open communication pathways between areas above and below the injury site.
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MACROPHAGE THERAPY:
Drs. Eti Yole, Nachson Knoller, (Israel), and Sir Jacques Brotchi (Belgium) summarized Proneuron Biotechnologies' efforts to use activated macrophages (a white blood cell) isolated from patient's blood to minimize neurological damage after acute SCI. Although healing immune cells are scarce in the "immune-privileged" central nervous system, Proneuron has circumvented this limitation by incubating the patient's macrophage-containing blood with skin tissue. The isolated macrophages are then surgically implanted into the spinal cord within 14 days of injury. By mediating protective immune responses, these activated macrophages promote functional recovery.
Phase 1 clinical trials showed no adverse treatment effects. Functional improvement was measured using the American Spinal Injury Association (ASIA) assessment standards. Of the eight patients treated (2 cervical and 8 thoracic injuries), three improved from ASIA A to C (complete injury to partial motor and sensory recovery). Of the remaining ASIA A patients, three showed improvements in sensory scores and nerve conduction. Proneuron has initiated a much larger phase II clinical trial that will recruit 61 patients at five treatment sites: Sheba Hospital (Israel), Craig Hospital (Colo.), Mt. Sinai (N.Y.), Kessler Rehabilitation (N.J.), and Shepherd Center (Ga.).
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CONCLUSION:
As reflected by symposium presentations, the once considered insurmountable barriers to restoring function after acute or chronic SCI are gradually being eroded in many ways. More importantly, over time, there has been a cumulatively huge shift in the attitude of the inherently conservative scientific community. Namely, SCI is no longer automatically a life sentence of paralysis without parole but a neurological disorder amenable to function-restoring therapies. This shift in the scientific collective consciousness by itself will greatly accelerate the development of real-world therapies.
Spinal Cord Patients Walk Again - Research Summary
Ivanhoe Newswire
BACKGROUND: Each year, there are 7,800 spinal cord injuries in the United States. The majority (44 percent) are caused by motor vehicle accidents. Other common causes of spinal cord injuries include falls, sports, and acts of violence. The spinal cord does not have to be severed in order for a loss of function to occur. In fact, in most people with SCI, the spinal cord is intact, but the damage to it results in loss of functioning. There are two types of SCI -- complete and incomplete. A complete injury means that there is no function below the level of the injury -- no sensation and no voluntary movement. Both sides of the body are equally affected. An incomplete injury means that there is some functioning below the primary level of the injury. A person with an incomplete injury may be able to move one limb more than another, may be able to feel parts of the body that cannot be moved, or may have more functioning on one side of the body than the other. Spinal cord injury victims are often confined to a lifetime in a wheelchair.
ON THEIR FEET: Functional electrical stimulation is now helping people with spinal cord injuries get back on their feet. The technology consists of a receiver, an external antenna, wires and electrodes on the muscles. When the patient pushes a button on an external controller, the electrodes are activated and cause the muscles to contract or relax in an organized fashion. This allows the person to stand up and, using crutches and braces, support themselves enough to get out of their chair, move across the room, and even climb stairs.
While the procedure has been available for adults, it is only now that doctors are treating children with FES. The problem has been a lack of understanding as to how the system would work in a person whose body is still growing and changing. Researchers from the Philadelphia Shriners Hospital first tested the technology in animals and are now treating patients. So far, the results have been encouraging.
WHO IT HELPS: The FES technology is intended for use in anyone who wants the ability to stand upright, whether it be for better mobility or to fit in with friends. It can be used on anyone who has live nerves in the legs meaning they still have spasms. About 10 percent of spinal cord injury patients do not have these spasms and the system will not work for them. Because the muscles are constantly contracted when the technology is activated, the patient often experiences a feeling as if they've been exercising. This is the only limitation placed on how far they can go using it.
FUTURE: Randal Betz, M.D., chief of staff at the Philadelphia Shriners Hospital, says this technology will only continue to improve. In the future, there will be systems with 24 channels so that it can control other functions such as the bladder and bowel functions. The next phase of the technology, which is being developed with a company in Australia, will have sensors that will turn the muscles on and off when needed, which will reduce the fatigue experienced by patients.
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If you would like more information, please contact:
Therese Johnston
Research Associate
Shriners Hospital for Children
(215) 430-4089
Last updated 7/7/2003.
This article can be accessed directly at:
http://www.drkoop.com/template.asp?page=newsDetail&ap=93&id=8006503
What is Project Walk™?
Project Walk is an intensive exercise program for people with spinal cord injuries and a goal of full recovery. Project Walk was developed through non-traditional methods by non-traditional specialists. Instead of doing what they were told to do or what was considered right, Ted and Tammy had the freedom to create and learn and to listen to their client's bodies and what their bodies were saying. Each new client brings new challenges and with each new challenge the program evolves and improves. Because each individual is different, there is no set program protocol. There is only a basic guideline to go by, the rest is following the client's lead. What's exciting is that each client in the program is progressing basically along the same lines. And this is what we are trying to prove -- that with our method, we can reproduce results and recovery is possible.
Healing powers of CannabisBut the drug may have positive effects for some. Marijuana is thought to dull chronic pain and may ease the symptoms of multiple sclerosis (MS), an incurable disease of the nervous system that causes spasms, pain and tremor.
In a recent large-scale trial, 60% of MS patients who took synthetic cannabis said it helped their mobility and eased their pain and muscle stiffness. "It doesn't suit everyone, but it does suit some," says Clare Hodges, MS sufferer and founder of the Alliance for Cannabis Therapeutics, a pressure group that lobbies for the medicinal use of marijuana.
About 10,000 seriously ill patients in Britain use cannabis to control their symptoms, says Hodges. Sufferers tend to smoke or eat the drug.
My Letter to the editor after being snubbed on Super Sunday
Jim,
I would like to thank you for taking the time to talk with me last week. I have to admit I was disappointed to not see anything in Sunday's paper. I can understand it was Super Sunday, it really isn't a very urgent issue, and quite frankly the numbers just aren't there. It also made me realize my advocacy skills need a lot of work, the main thing is you can't be a passive advocate. It was Super Sunday, you'd be surprised how many SCI's are football fans, actually quite a few of them were top notch high school football players who in a split second were turned into spectators. To a large number there 'Teams' are a driving force in their rehabilitation. Hell when I was in rehab we got Super Sunday off. Super Bowl parties are still a lot of fun drink some brews, munch, running to the bathroom during timeouts is kinda hard though!
And it isn't real urgent, it's not like even with all the funding they would have a cure tomorrow or even five years from now what's the rush? People need to ask that question when they or a loved one is in the emergency room or recovery struggling to breath not being able to move while a team of doctors stands around saying we can't do anything we don't know enough about the Spinal Cord, but get ready we are going to put you through 6 weeks of some of the most grueling therapy you'll ever experience, maybe you'll regain some function but don't bet on it.
Sad story huh, makes you feel sorry for them, but your just glad it's them and not you.
There are 500,000 Americans ( that is just the injured, it doesn’t count those with diseases of the spinal cord!) out there that knew it would never happen to them, they didn't do dangerous things, they weren't risk takers, they didn't run with the wrong crowd. The one thing 99% of them will tell you is it happened in the blink of an eye, a heartbeat, a New York second! All it took was a slip, a patch of black ice, a stray bullet, an intentional bullet, an angry spouse, or co worker, even just lifting something can change a life forever. My point is able bodied people need to be just as concerned about a cure as injured people are, because but for the grace of God…..no amount of precautions or diligence can guarantee it won't happen to you!
Sure I was disappointed but being in a chair you learn to gain strength from adversity & setbacks. I need to become more involved, I will go to the support meeting this Thursday, I'll tell the members how they were snubbed by all the editors and writers of the Journal except for one, that none felt getting the message out was important enough. I'll also tell them about the congress women/men, representatives that never bothered to reply. I'll learn, they will learn because the numbers are there, that number gets larger everyday, we won't be ignored and take it from some one that was bi-ped, you can't afford to ignore it if you wait until it happens to you to get involved then it's too late!
Thanks again Jim you were the only one out of about 30 to even reply.
Because I'm just learning advocacy and letter writing I would very much appreciate your input
Jan,25,2004
Self-assembling scaffold for spinal-cord repair
'Liquid' bridge could help severed nerve cells grow.
23 January 2004
HELEN R. PILCHER
It may well be the smallest scaffolding in the world, and the easiest to set up. Researchers have devised a tiny self-assembling structure that they hope will help repair damaged spinal cords.
Every year in the United States alone, about 15,000 people damage their spines. Few recover fully as it is difficult for damaged nerves to grow across the gap in a severed spinal cord.
Researchers have tried to build bridges across these gaps, so that nerves can grow. Most of these are made out of a solid material such as collagen, but require invasive surgery that can cause extra trauma to the injury.
Samuel Stupp and colleagues from Northwestern University, Chicago have now found a way to build a bridge out of liquid instead1.
When the solution is injected into a damaged rodent spinal cord, it turns into a gel-like solid, says Stupp. The scaffold is designed to disintegrate after four to six weeks, hopefully leaving healthy spinal cord behind.
Self-assembly
The liquid is made up of negatively charged molecules. Normally, they repel one another and keep the substance in liquid form. But when the fluid encounters positively charged molecules - such as the calcium or sodium ions found in living tissue - they clump together. "The effect happens almost instantly," says Stupp.
The molecules are designed to aggregate in a particular way, forming a mass of tiny, hollow tubes. Each tube is about 5 nanometres wide - 10,000 times smaller than the width of a human hair - and several hundreds of nanometres long. The structure is porous, allowing nerve cells to grow through and around it.
The team also laced each molecule in the liquid with a tiny protein fragment that nerve cells can recognize and latch on to. This may aid the development and growth of nerve cells, speculates Stupp.
It's a sophisticated system, says David Mooney, who studies tissue engineering at the University of Michigan. It allows you to control the physical and biological make-up of the structure.
Bridging the gap
But there are many hurdles to overcome. Even with the chemically laced scaffolding in place, nerve cells may still struggle to regrow.
After a spinal-cord injury, the surrounding cells multiply to form a dense scar, explains spinal-cord researcher Elizabeth Bradbury from Kings College London. This barrier is impenetrable to nerve cells, so enzymes that can break it down may also need to be added, she says.
To give spinal-cord repair an extra boost, the team also tried introducing fresh nerve cells into the system. When they added stem cells - cells that can turn into other, specific types of cells, such as nerves - to the scaffolding solution, they turned into neurons and began to grow within the solidified bridge. The team plans to try to do the same thing in damaged rodent spinal cords.
Research into spinal cord repair has made enormous progress in recent years. Spinal Research now hopes for the regeneration of four centimetres of spinal cord in a paralysed person. Those four centimetres could potentially help a seriously paralysed person breathe unaided, or regain the use of his or her arms.
The neurons forming the spinal cord are highly vulnerable to damage if vertebrae of the spinal column are subjected to a severe shock or impact. Unlike nerve fibres in other parts of the body, they do not have a natural ability to regrow if they are cut or damaged. Spinal cord neurons do not repair themselves.
A number of complementary research routes show particular promise for the successful treatment of spinal cord injury. Spinal Research calls them the Routes to the 4cm Future and they form the basis of research leading to the planned clinical trials.
Minimising the initial damage - Neuroprotection
Most spinal injuries do not completely sever the spinal cord outright. In most cases, some neurons in the surrounding area remain intact, at least initially.
However, when neurons in the spine die, they send out signals that cause neighbouring, uninjured neurons to die. This enlarges the damaged area and can double the size of the affected area in the first few hours after injury. It also causes scar tissue to accumulate at the injury site. Scientists are now investigating ways of reducing the spread of secondary damage at an early stage – soon after the injury has occurred, thus reducing the scale of the injury and its long-term consequences.
Removing barriers – Chondroitinase treatment
Chondroitinase is an enzyme that partially removes the otherwise impenetrable barriers formed by the scar tissue around a spinal cord injury, allowing regenerating nerve fibres to pass through.
In the months following injury to the spinal cord, the loss of neurons is accompanied by the formation of scar tissue that gradually fills the damaged area.
Scar tissue is a major obstacle to regeneration because it contains several molecules that inhibit neuronal growth. With backing from Spinal Research, researchers have dissolved away vital parts of these growth inhibitors. Consequently, neurons have grown through the scarred region to undamaged tissue beyond.
Neuronal growth of up to 4mm has been measured in laboratory models, accompanied by increases in sensation, muscle coordination and walking.
Combating blockers – Counteracting Nogo
Antibodies have been developed to counteract the effects of Nogo, a family of molecules that prevent the regrowth of nerve fibres in the spinal cord.
Preventing inhibition of regrowth
In mature mammals, the brain and spinal cord contain powerful inhibitory factors that prevent nerve growth. These factors are designed to have a protective role, preventing nerves from growing inappropriately after normal neuronal connections have developed. Following injury, however, these same inhibitory factors prevent repair processes from starting. Scientists have now developed an antibody that combines with Nogo and neutralises it before it interacts with neurons. This prevents these inhibitory effects and increases neural regeneration.
Filling the gap – Tissue engineering
Newly developed biocompatible materials can form a bridge across the damaged region and provide the optimum environment for regrowth of nerve fibres, blood vessels and supporting tissues. Tissue grafts help fill the cavities inside the spinal cord that are created by injury.
This approach aims to bridge the gap between the damaged ends of neurons on either side of a spinal cord injury. It does this by transplanting artificial guidance channels into the spinal cord. These provide a physical support along which neurons can regrow. The guidance channels direct growth across the damaged area and protect neurons from barrier-forming scar tissue. Incorporating growth factors into the new tissue ‘scaffolding’ can further boost the regeneration of neurons.
Nurturing regrowth - Olfactory glia
Olfactory glia are unique cells that exist in the olfactory system (responsible for the sensation of smell), where they guide and protect newly-forming nerve fibres. When transplanted into the damaged spinal cord, they aid the regeneration of nerve fibres.
In humans, the nerves that transmit the sensation of smell from the nose to the brain - unlike those in the brain and spinal cord - are replaced naturally throughout life. They also regrow after injury. Olfactory nerves do this because they are surrounded by specialised cells, called olfactory glia, which form a protective myelin coating around the nerves.
Olfactory glia do not occur naturally in the spinal cord. However, with funding from Spinal Research, laboratory researchers have transplanted olfactory glia into spinal cord injuries. Results have confirmed that the glia have a regenerative effect on the damaged spinal cord.
In addition, myelin is essential for the rapid transmission of nerve signals. It can degenerate after spinal cord injury, with the result that undamaged neurons no longer function efficiently. Therefore, using olfactory glia to restore the myelin coating could boost the performance of the neurons that remain following injury.
Stimulating and guiding – Neurotrophic factors
Neurotrophic factors (also called growth factors) are molecules that are involved in stimulating and guiding the growth of nerve fibres, encouraging regeneration in damaged areas of the spinal cord.
Scientists funded by Spinal Research are finding ways to make the damaged ends of neurons regenerate and form sprouts that grow through the damaged region. They are using growth factors to do this.
In the course of normal human development, growth factors play a vital role. They stimulate the cells that are programmed to form neurons in the spinal cord, causing them to divide and grow. Many growth factors also attract growing neurons to areas that contain the highest concentrations of growth factor, thereby directing neurons to their appropriate target regions.
Spinal Research is funding investigation into the most effective growth factors and the best ways to introduce them into the injured spinal cord.
Replacing damaged cells – Stem cells
Stem cells have the potential to develop into every type of cell in the body. In future, stem cells might be used to replace the neurons and glial cells that die after spinal cord injury.
Human life begins as a single cell that is formed when the father's sperm fuses with the mother's egg. This initial cell then divides to form a ball of cells: the cells on the outside of this ball form the placenta, whereas those inside the ball are embryonic stem cells. All of the cells in the body, from liver cells to neurons, come from the division of embryonic stem cells.
Scientific research using embryonic stem cells is still at quite an early stage. Obviously there are ethical considerations with any research that involves cells from embryos, but research for therapeutic purposes - such as the development of treatments for spinal cord injury - is legally allowed. Using cells from adults would overcome ethical concerns, but research on adult stem cells is much less advanced.
Stem cells hold great potential for the treatment of spinal cord injury. Because they can develop into every type of cell, they could, in principle, be used to replace all the damaged tissue in the spinal cord. However, scientists do not yet understand how to control stem cells and make them turn into the required cell types. At present stem cells that are transplanted into spinal injuries mostly develop into the cells that make scar tissue.
Spinal Research supports stem cell studies. It is not directly funding projects on this topic at present because priorities are in other areas, but expects to do so in the future.
New Hope for Severed Spine
A team from Purdue University has reported that for the first time, electrical nerve impulses have been restored in the severed spinal cord of a mammal. The Purdue Press release states that the scientists isolated spinal cords removed from adult guinea pigs. They fused the cut nerve fibers using a polymer called PEG. Electrical impulses were restored in all of the guinea pig cords used in the study. The repaired spinal cords transmitted between 5 percent and 58 percent of pre-cut impulses.
A percentage of the fibers in the severed spinal cords were reconnected, however scientists did not reconnect all the fibers. Researchers demonstrated this by passing special dyes through the repaired nerve fibers. "If you have even 5 percent of the nerve fibers carrying nerve impulses, you'll get significantly more than 5 percent back in terms of restored behavior," says Richard B. Borgens, professor of developmental anatomy at Purdue. He and his colleagues at the Center for Paralysis Research in the School of Veterinary Medicine reported their findings at the annual meeting of the Society for Physical Regulation in Biology and Medicine. "This technique may be a revolutionary new way of dealing with injuries to the nervous system," Borgens says. "It's too soon to know whether it would help patients with old injuries, but it is likely to be useful in treating recent injuries." Borgens and his team are now testing the procedure in live animals. They plan to conduct clinical trials in natural cases of paraplegia in dogs early in 1999, but human clinical trials are at least two years away.
The isolated spinal cords remain viable for about 36 hours after removal. Borgens says the results of studies in live animals will shed more light on how permanent the new technique might be. The scientists applied polyethylene glycol, or PEG -- a nontoxic, water-soluble polymer used in medicine and cosmetics -- across the region of the guinea pig's spinal cord that had been severed but gently pressed back together. PEG was applied for two minutes, then removed. The polymer "fused" the membranes of a significant number of nerve cells together, making them continuous once again. The researchers then applied a small electrical current to one end of the cord to stimulate nerve impulses . Between five and 15 minutes after the PEG application, nerve fibers were repaired, allowing some impulses to reach the other end of the severed cord in 100 percent of the cases. "The technique is called fusion technology," Borgens explains. He compares the procedure to repairing a garden hose -- the rubber is the cell membrane and the water inside is the salty material, called cytoplasm, found inside all cells. "If we cut the hose and just hold the two ends tightly together, they're not going to reconnect or function as a hose. But if we add this special molecule, PEG, the 'rubber' melts a tiny bit on each side and literally fuses the 'hose' back together." Borgens says the technique also can repair crushed nerve cells that develop holes in their membranes.
Functional Neuromuscular Stimulation (FNS)-Assisted Walking:
Majority participation (25/35 paraplegic subjects) in multi-center trial of Parastep® 1.
This trial led to designation of Parastep as the first FDA approved, commercial computer-assisted walking system. The system uses electrodes taped on the skin of the legs and back to allow persons with complete paralysis to stand and walk for limited distances.
Extensive testing at the Miami Project defined the benefits and shortcomings of Parastep® 1. The researchers are testing different applications of the system to enhance its cardiovascular and conditioning benefits.
Our scientists have continued to use the Parastep system to evaluate protocols beyond the scope of the FDA-trials. The Miami Project's controlled experiments demonstrated that Parastep training allows many subjects to walk for distances of more than a mile, and improves leg muscle mass, cardiovascular fitness and psychological measures.
Advances Made in Treatment of Spinal Cord Injuries
While more than 11,000 people sustain spinal cord injuries (SCI) each year, many Americans first learned about them when actor Christopher Reeve was paralyzed. That was six years ago.
In that short time span, tremendous advances have been made in improving the quality of life for individuals with SCI through better treatment and new rehabilitation therapies.
"Most of the care for acute and long-term spinal cord injuries is provided by specialists in PM&R," explains David Chen, MD, a PM&R physician and director of the spinal cord injury program at the Rehabilitation Institute of Chicago. "Often we become an injured patient's primary care physician, because we are more familiar with the unique nuances and secondary issues of the condition."
This "familiarity" has led to significant advances in both technology and techniques that will maximize the capabilities of people with spinal cord injuries in all aspects of their lives - physical, emotional, social and vocational.
Better Technology
Among the many technological advances are improved, lighter weight wheelchairs that are easier to maneuver. "These significantly improve the quality of life from a practical, everyday standpoint of being comfortable and getting around," states Steven Kirshblum, MD, director of the spinal cord injury and ventilator program at the Kessler Institute for Rehabilitation in New Jersey, who treats Christopher Reeve.
Kirshblum adds that new wheelchairs are being developed that can actually climb stairs. "This will help overcome some of the environmental and architectural barriers that can exist to both work and social opportunities."
Voice-activated computer technology is further enhancing the lives of those living with SCI. The assistance of a computer can make certain activities less exhausting. In some cases, voice-activated technology has made many of the daily tasks of living and working possible for the very first time - such as answering and dialing the phone or using a computer to e-mail messages and pay bills.
Although still being studied, treadmill-assisted walking may also greatly improve ambulation. This therapy is based on the theory that a central pattern generator (CPG) resides in the spinal cord that controls rhythmic locomotion patterns such as walking or running. Repetitions of walking are believed to reactivate the CPG so the injured patient can re-learn the stepping mechanism and walk.
"A lot of PM&R physicians are involved in this therapy because we know about this neurologic condition and how the body responds to activity," reports Chen. "I evaluate how each patient responds to this therapy to see if there is improvement or if their spasticity worsens and we need to change medication or alter bracing for their limbs."
Stimulating News
New electrical stimulation devices that are implanted in the body have recently been developed that can restore some hand movement. These allow people with SCI to write and feed themselves. Other electrode implants can help better control bladder and bowel function. Electrical stimulation devices can also assist with breathing so that some people do not have to be on a ventilator.
And developments in new and safer techniques and medications for erectile dysfunction have enhanced the quality of life for many individuals and couples. "These have been studied and are now approved for clinical use," says Kirshblum. "There are also greatly improved techniques in fertility that allow those with SCI to have children."
http://www.projectwalk.org/