Vol.4, # 2
January 13, 2007

Q: Do nerves regenerate? - Layperson

A: Once thought impossible, nerves can regenerate to one degree or another under very restricted and limited conditions, in all living organisms, the young more so than the old.For this to occur, the proper enzymes, nutrients, an electrical stimulation must occur, either unaided or with medical intervention. Scar tissue must be eliminated and inflammation regulated-either eliminated or encouraged, depending where, in the healing process, it occurs.

At the core of the human nervous system, a control system of the body, is the central nervous system (CNS), which is composed of the brain and spinal cord. Using electrical signals that travel from the CNS through the peripheral nervous system (PNS), the brain controls effector cells, which carry out the physiological responses "requested" by the brain. Thus, the nervous system is a "wired" communication system of the body.

Anatomically, the fundamental cell of the brain is the neuron, which consists of a cell body, branch-like extensions off the cell body called dendrites, and at least one longer extension off the cell body called an axon. The dendrites conduct signals from their tips toward the neuron cell body whereas the axon carries messages away from the cell body toward the terminal end of the axon. The neuron communicates with other cells, such as effector cells, through the distal tips of the axon.


Diagram of a neuron.
Source: http://www.ccs.neu.edu/groups/honors-program/freshsem/19951996/cloder/neuron.html

Nerves are bundles of axons from different neurons that carry signals in the same direction; nerves are the essential intermediary connecting the brain to effector cells. Thus, if nerves are severely damaged, the signal between the cell body and effector cells is interrupted, and neurons are unable to convey effective "requests," such as a muscle movement. This is similar to cutting an electrical cord connecting a lamp to an outlet.


Diagram illustrating the spinal nerves and their function
Source: http://www.spinalinjury.net/html/_spinal_cord_101.html

What damages nerves?

Nerves can be damaged either through trauma or disease. Nerve trauma may be incurred through motor vehicle accidents, severe falls, lacerations, and typing. Traumatic nerve injury, such as carpal tunnel syndrome, is caused by the compression of nerves. Other trauma, such as falls and motor vehicle accidents, may lead to the severance of nerves. Diseases that damage nerves include multiple sclerosis, diabetes, spina bifida, and polio. Multiple sclerosis, for example, causes the breakdown of the insulating myelin surrounding axons.

The most dramatic and serious nerve damage occurs to the spinal cord. Damage to the lower spinal column may lead to paraplegia, paralysis of the lower extremities, and damage to the upper spinal column may lead to quadriplegia, paralysis of all four extremities. The incidence of spinal cord injury in the US is 11,000 per year and the prevalence is 250,000 to 400,000. The cost to support a patient with a spinal cord injury through his or her lifetime is estimated to cost between $400,000 to $2.1 million depending on the severity of injury.

Why can't the CNS heal damaged nerves itself?

Unlike a cut that heals, the central nervous system has limited ability to fix its damaged nerves, in contrast to the peripheral nervous system. When parts of the central nervous system are critically injured, the CNS cannot generate new neurons nor regenerate new axons of previously severed neurons. Severed CNS tips initially try to grow, but eventually abort and ultimately completely fail to regenerate. A look into this mechanism will reveal much about how and why the CNS works the way it does.

Remarkably, almost 90% of cells in the CNS are not even neurons. Rather they are glial cells, which play an important role in supporting neurons both physically and metabolically. They maintain the extracellular environment to best suit and nourish neighboring neurons. The CNS and PNS have two distinct types of glial cells, and they are what accounts for the discrepancy in regenerative ability.

In the PNS, the glial cells are Schwann cells that don't inhibit axon regeneration. Their sole function here is to produce myelin to facilitate more effective transportation of neurotransmitters.

In the CNS, there seem to be two "glial culprits" that inhibit axon regeneration. These are oligodendrocytes and astrocytes. Both play key roles in CNS support and metabolism. It is logical to ask hear, "why on earth would the body ever want to inhibit regenerative ability?" The body has a good answer.

This growth-inhibiting action helps enormously in stabilizing the outrageously complex CNS. This highly organized complex must be maintained, and the growth-inhibitors provide a cellular 'scaffold' so that neurons only sprout to where they are intended. The inhibitors effectively lock the connections into place. Without these proteins, the CNS may not be able to organize itself and work properly. The tradeoff, though, is that the CNS has no ability to regenerate itself in the event of injury. Since the PNS is capable of regeneration, it is evident that cellular mechanisms exist to promote nerve regeneration.

A team of scientists at UCSF has made a critical discovery that may help in the development of techniques to promote functional recovery after a spinal cord injury.

By stimulating nerve cells in laboratory rats at the time of the injury and then again one week later, the scientists were able to increase the growth capacity of nerve cells and to sustain that capacity. Both factors are critical for nerve regeneration.

The study, reported in the November 15 issue of the Proceedings of the National Academy of Sciences, builds on earlier findings in which the researchers were able to induce cell growth by manipulating the nervous system before a spinal cord injury, but not after.

Key to the research is an important difference in the properties of the nerve fibers of the central nervous system (CNS), which consists of the brain and spinal cord, and those of the peripheral nervous system (PNS), which is the network of nerve fibers that extends throughout the body.

Nerve cells normally grow when they are young and stop when they are mature. When an injury occurs in CNS cells, the cells are unable to regenerate on their own. In PNS cells, however, an injury can stimulate the cells to regrow. PNS nerve regeneration makes it possible for severed limbs to be surgically reattached to the body and continue to grow and regain function.

Regeneration occurs because PNS cell bodies are sensitive to damage to their nerve processes, and they react by sending out a signal that triggers the nerve fibers to regrow, explains Allan Basbaum, PhD, senior study author and chair of the UCSF Department of Anatomy. "Apparently this communication doesn't take place within the CNS."

Scientists do not yet know the biochemical cause for the difference, he adds.

The traditional scientific approach in efforts to enhance CNS regeneration is to manipulate the biochemical environment of the cells at the site of the spinal cord injury, according to Basbaum. Instead of this type of investigation, Basbaum's team used nervous system manipulation techniques to apply the principles of PNS cell growth capability to CNS cells.

The researchers took advantage of an unusual class of nerve fibers that has both a PNS and a CNS branch. Previously, the researchers had shown in animal studies that an injury made to the peripheral branch prior to a spinal cord injury provided the essential communication signal that enabled the CNS branch to grow. But this only worked if the PNS injury--which served as priming for CNS cell growth--was made at least a week before the CNS injury. "Clearly this would have no utility in clinical situations, where treatments cannot be made in anticipation of spinal cord injury," says Basbaum. Another challenge the researchers faced was stimulating CNS cells to grow beyond the injury site and into healthy tissue, which is essential to help regain function.

"A PNS injury at the time of spinal cord damage will only promote growth of nerve fibers into the spinal cord lesion, but not into the tissue beyond it. This is because growth capacity is enhanced, but it is not sustained," he explains. In the new study, researchers evaluated the effect of two peripheral nerve lesions (injuries) in animals with spinal cord injury. One lesion was made at the time of the cord injury and a second was made a week later. Both lesions were located in the animals' sciatic nerve, which is part of the PNS.

The researchers found that the two "priming lesions" not only promoted significant spinal cord regeneration within the area of the spinal cord injury, but more important, the regenerating axons grew back into normal areas of the spinal cord, where the hope is that functional connections can be reestablished. Axons are the long, fragile, fibers that conduct impulses between nerve cells in the brain, spinal cord and limbs.

"Getting the growth beyond the lesion is key. If we can get those axons to grow even a few centimeters past the lesion, they can start sending signals and developing new circuits throughout the body," says Basbaum. Basbaum adds that timing is critical for successful nerve regeneration. "There is a window of opportunity just after the injury when the potential for growth through and beyond the lesion is greatest. If we wait too long after an injury, the cells revert back to their normal, no-growth state. Plus, scar tissue begins to form, making growth difficult." "These findings give us hope. The nervous system is capable of being modified to a level where we can achieve nerve fiber growth. Ultimately, the goal is to promote growth and sustain it long enough for recovery of movement to occur in spinal cord injury patients," he concludes. Study co-authors include first-author Simona Neumann, PhD, and Kate Skinner, MD, both of UCSF. The research was funded by the Roman Reed Spinal Cord Injury Research Fund of California and the National Institutes of Health.

UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.

Reversing brain and spinal cord injuries may soon be possible with the discovery of a gene and protein responsible for stopping axon regrowth, Yale researchers say.

Brain and spinal cord axons can grow after injury if provided with an adequate environment, but the natural adult brain environment contains substances which inhibit axon regeneration. One of these inhibitors is the Nogo protein.

"We have identified the gene and protein responsible for this Nogo activity," said Stephen M. Strittmatter, M.D., associate professor of neurology and of neurobiology at Yale School of Medicine. "Our work suggests that the Nogo protein is an important and selective blocker of axon regeneration in the brain after central nervous system injury."

The central nervous system (CNS) of warm-blooded vertebrates does not support nerve regeneration, in contrast to the regenerative potential of the peripheral nervous system (PNS) . After injury, CNS axons degenerate resulting in permanent loss of nervous function. This phenomenon has clinical implications for humans and the study of the biochemistry involved in axonal regeneration is of considerable biomedical interest. In cold-blooded vertebrates the CNS shows marked regenerative potential. The teleost and the amphibian optic nerve have been extensively used as model systems of successful regeneration in the CNS . After injury, the axons of the retinal ganglion cells (RGCs) regenerate and reconnect with their targets in the tectum . Biochemical studies with these systems has led to the identification of several proteins that are induced in neurons that are regenerating their axons, which therefore may play a role in axonal regeneration. These proteins are known as axonal growth associated proteins (abbreviated as GAPs) and their study is of great importance to understand the regeneration process, the differences of capacities for regeneration or even for interventions aimed at improving the regeneration response They include cytoskeletal proteins , cell adhesion proteins , ion channels , transcription factors and other proteins of less well defined function like GAP-43  and RICH proteins. 

RICH proteins represent a new family of GAPs that was initially shown to be induced in regenerating retinal ganglion cells (RGCs) of goldfish. In goldfish there are two acidic proteins that were designated p68/70 upon their discovery, to reflect their apparent molecular weight. The protein doublet was purified from brain tissues and was shown to represent two related proteins partially associated to the plasma membrane. The purified proteins were used to generate partial peptide sequences that were used to clone cDNAs encoding p68/70 related proteins. Sequence analysis showed significant homology to a marker enzyme of mammalian myelin: CNPase (2',3'-cyclic-nucleotide3'-phosphodiesterase). Consequently, the encoded proteins were re-designated gRICH68 and gRICH70 (for goldfish Regeneration Induced CNPase Homologs of 68 and 70 kDa). The recombinant proteins were expressed both in prokaryotic and eukaryotic systems and it was shown that they possess
2',3'-cyclic-nucleotide 3'-phosphodiesterase activity, identifying the gRICH proteins as novel non-mammalian members of the CNPase family.        

A highly specific polyclonal antibody was generated against recombinant gRICH and was used to confirm the identity of the two proteins with the p68/70 doublet components. The antibody was also used in immunodepletion experiments to suggest that these gRICH proteins are the major 2',3'-cyclic-nucleotide 3'-phosphodiesterases in goldfish retinas.  Recently, a cDNA encoding a RICH protein has been cloned from a zebrafish library. Both the corresponding mRNA and protein (designated zRICH) are induced during regeneration of the optic nerve in zebrafish. Site directed mutagenesis has identified two residues (H334, T336) in zRICH that are necessary for catalytic activity. The zebrafish is emerging as a model system for classic and molecular genetic studies, offering great potential for future studies aimed at discovering a role of these proteins in nerve regeneration.   

Published in the January 27 issue of Nature, Strittmatter's study shows that Nogo protein generated in the laboratory stops axon growth. In addition, the protein is found exclusively in those areas of the brain which are most hostile to axon growth. Future experiments will determine whether this is the major inhibitor of axon regeneration in the brain or if it is one of several inhibitors.

After many adult nervous system injuries, the nerve cells survive but their connecting axons are severed and function is lost. Outside the brain and spinal cord, these connections usually grow back and recovery is excellent.

Inside the brain and spinal cord, very little axon regrowth occurs after injury and the clinical prognosis for recovery of function is poor. A clear example of this is human spinal cord injury.

In addition to identifying the gene and protein, the team also found that the inhibitory activity is localized to a discrete portion of Nogo. Because this inhibitory portion is less than 10 percent of the entire Nogo protein, Strittamatter says, the identification and design of inhibitors of Nogo action should be greatly facilitated.

"If those inhibitors based on Nogo can be developed, the failure of axon regeneration and functional recovery after many brain and spinal injuries might be reversed," said Strittmatter.

Strittmatter's research team in the Department of Neurology at Yale included Tadzia GrandPre and Fumio Nakamura, M.D. The work was completed in collaboration with Timothy Vartanian, M.D. of the Department of Neurology at Beth Israel Deaconess Medical Center Harvard Institutes of Medicine

New Haven, Conn. Yale researchers have developed a synthetic peptide that promotes new nerve fiber growth in the damaged spinal cords of laboratory rats and allows them to walk better, according to a study published Thursday in the journal Nature.

The finding could lead to the reversal of functional deficits resulting from brain and spinal cord injuries and caused by trauma and stroke, or brought about by degenerative diseases, such as multiple sclerosis.

The lead author of the study, Stephen Strittmatter, M.D., associate professor of neurology and neurobiology at Yale School of Medicine, said the study confirms which molecules block axon regeneration in the spinal cord and shows that a peptide can promote new growth. Axons are the telephone lines of the nervous system and carry a nerve impulse to a target cell.

"One of the prominent inhibitors is Nogo and we developed a way to block Nogo action with a peptide that binds to the Nogo receptor and prevents it from doing its normal job," Strittmatter said. "There is no drug used today to promote axon recovery in humans, so it is hard to predict how well this drug will work in humans."

He said the laboratory rats were administered the peptide for four weeks through a catheter inserted into the spinal canal. A number of nerve fibers did grow back and the rats were able to walk better than without the treatment.

Before moving to human trials, Strittmatter said researchers first must determine whether the synethetic peptide can promote nerve fiber growth in animals weeks and months after injury and whether the compound is effective and safe for use in humans.

"There is some reason to think that the peptide might promote growth in older injuries because some damaged nerve fibers in the brain and spinal cord just sit there," he said. "If we had some way to block these inhibitors the nerve fibers might grow back again."

The paper is the third that Strittmatter has published in Nature about this research. The first paper described the Nogo protein. The second paper detailed the receptor through which Nogo acts. This newest data demonstrates how to block the interaction and how to reverse its function pharmacologically.

The synthetic peptide Strittmatter and his colleagues developed is 40 amino acids long and acts as an inhibitor at the Nogo receptor site.

Co-researchers included Tadzia GrandPre, a graduate student, and Shuxin Li, a postdoctoral fellow.

Turning off a well-known chemical switch may allow severed nerves in adult mammals to regenerate, according to a report in this week'sScience. By jamming the epidermal growth factor (EGF) receptor, the authors blocked harmful signals known to limit repair of damaged axons in the central nervous system. Their finding points to a promising new target for restoring neural function following injury, they say.
 
Previous research that sought to explain why mammalian axons fail to regenerate in the wounded brain or spinal cord found several inhibitory cues that prevent healing. The culprits include proteins associated with myelin and proteoglycans released by the glial scar that forms after neural injury.
 
In a search for a signal that might override this chemical blockade, a group led by Zhigang He of Children's Hospital in Boston, Mass. cultured neurons on a myelin substrate. They screened approximately 400 candidate compounds, looking for those that could promote growth in this hostile environment. When exposed to a subset of the molecules, neurons sprouted extensions called neurites, the first step to extending axons. That subset of molecules shared the ability to shut down the EGF receptor. Neurites also grew in the presence of two well-characterized EGF receptor inhibitors, but not a control compound.
 
"It's surprising finding," said Martin Schwab of the University of Zurich, since activation of the EGF receptor is normally associated with proliferation and growth of cells. Schwab has characterized the signaling pathways of myelin proteins but was not associated with this study. In this case, "the EGF receptor is a bad actor," said Marc Tessier-Lavigne, Senior Vice President for Research at Genentech in South San Francisco, Ca. and a co-author of the paper. "Activation of the receptor is involved in blocking things, not in stimulating growth," he said. "It's an unexpected role for the EGF receptor."
 
Stephen Strittmatter of Yale University School of Medicine in New Haven, Ct., who first described one of these inhibiting proteins, called Nogo, points out that the connection between Nogo, its receptor and the EGF receptor remains to be worked out. "It is still perhaps a little unclear how the Nogo receptor couples to the EGF receptor and how that coupling is required for inhibition of axon growth," he said.
 
The authors found that cultured neurons bathed with inhibiting proteoglycans derived from glial scars also grew neurites when the EGF receptor was blocked. That's interesting because proteoglycans and proteins associated with myelin signal through separate biochemical channels, Tessier-Lavigne said. "The EGF receptor seems to be a point of convergence of these two disparate sets of signals," he said.
 
This common switch could be a potent new target for therapies aimed at repairing damaged nerves. "If with one manipulation – blocking the EGF receptor – you can block the actions of multiple factors, then you can hope to have a bigger effect than if you block any one factor or any one signaling pathway," Tessier-Lavigne told The Scientist.
 
"The beauty of this observation is that some drugs that will block this pathway have already been approved for the treatment of cancer," said Marie Filbin of Hunter College in New York City, who also works on axon-inhibiting proteins. "If further animal studies prove promising," she said, "the clinical work will move forward very quickly."
 
Genentech already sells an EGF-receptor-blocking drug called Tarceva, which is approved for the treatment of lung cancer, and plans to begin testing it on a mouse model of spinal cord injury, Tessier-Lavigne said. The scientists at the McKnight Brain Institute of the University of Florida have recently made three fundamental discoveries about the cellular and molecular mechanisms that regulate peripheral nerve regeneration:
  • An inhibitory component of the nerve sheaths restricts axonal growth;
  • Natural degeneration of injured nerve involving enzymatic degradation of the growth inhibitor is necessary to facilitate regeneration;
  • The inhibitor can be specifically inactivated by application of exogenous enzymes.
These scientific breakthroughs led researchers to develop several new patent pending technologies that will be incorporated into AxoGen’s product lines. AxoGen products will be the first to capitalize on the latent growth promoters present in peripheral nervous tissue.

New Understanding of Nerve Regeneration

AxoGen’s scientific team’s new discoveries improved understanding of the obstacles to nerve regeneration. The endoneurial sheath (including the basal lamina) surrounding the axon contains a potent promoter of axonal growth called laminin. AxoGen’s scientific team has learned that laminin activity is counterbalanced by an associated molecule that prevents the growth of axons in response to laminin. In a healthy nerve, this substance prevents axons from dysfunctional growth and sprouting. The endoneurial sheath, with its inhibitor substance, maintains homeostasis and suppresses the innate propensity of axons to sprout in the event of injury.

After injury to axons, it is essential that they regrow within the basal lamina of the endoneurial sheath. However, this requirement is challenged by misalignment of axons and sheath elements as a result of nerve transection. Growth-inhibitory substances are abundant and rapidly accumulate after injury. It follows that any misalignment of nerve microstructure (after injury and repair) forces regenerating axonal sprouts to immediately negotiate nonpermissive tissues which may severely limit their access to basal laminae in the distal nerve. AxoGen’s scientific team found that inactivation of the growth inhibitor by application of specific enzymes improved axonal regeneration through lesions and improved the outcome of conventional end-to-end repair of transected nerves.

AxoGen Nerve Regeneration

The first two above scientific discoveries led to the development of a processing compound that fosters nerve regeneration called nerve activator. This nerve activator is used in an injectable form for primary nerve repair, as well as, in the processing of activated nerve grafts. It inactivates the nerve growth inhibitor, thereby allowing the natural regenerative capacity of the injured nerve (i.e., by deinhibiting laminin activity) or nerve graft.

AxoGen Regeneration Processing

The third discovery led to a processing method by which the natural degenerative process could be replicated within a donor nerve graft in a controlled processing environment. This natural degenerative process primes the nerve graft for the axonal regeneration process and then the graft is frozen before storage for transplantation. AxoGen's graft processing renders the nerve acellular and eliminates the concerns of rejection and circumvents the need for immunosuppressants. The result of these patented processing steps is a remarkable increase in efficacy of nerve grafts and resurrects the promise of clinical nerve allografting.

Nerve regeneration after brain or spinal cord injury can be improved by dissolving the sugar chains found on the inhibitory protein molecules that fill the scar tissue. Neuroscientists at the Brain Repair Centre in Cambridge have discovered that by using a bacterial enzyme to dissolve the sugar they can significantly improve the regeneration of neurones (Nature Neuroscience 2001;4:465-6).

One of the reasons that neurones do not grow back after an acute injury is that the glial cell scar tissue becomes full of inhibitory molecules called chondroitin sulphate proteoglycans. These proteins, which are modified by the addition of sulphated sugar chains, prevent neurones growing back through the damaged area. Knowing that the sugar chains confer most of the inhibitory properties of these molecules, Dr James Fawcett and his team of neuroscientists in Cambridge have been looking at ways to chemically remove them.

Using a rat model of brain damage, the scientists investigated whether a bacterial enzyme called chondroitinase ABC would dissolve the sugar chains. They inflicted damage on the nigrostriatal system (the part of the brain damaged in Parkinson’s disease) and observed that the resulting scar tissue was accompanied by an increase in the amount of chondroitin sulphate proteoglycans at the site of the injury. They then infused chondroitinase ABC into the injured area and found that within a week the damaged axons that produce dopamine had regrown by up to 1 cm in length towards their original target, with evidence of axon terminals actually in the striatum itself. No regrowth of neurones was seen in the control rats.

Having shown that chondroitinase treatment promotes regeneration in this simple axon pathway, Dr Fawcett's team started a collaboration with Dr Elizabeth Bradbury at King’s College London to see whether chondroitinase ABC also works when applied to spinal cord injuries. In these experiments the damaged axons regrew to a length of 2 cm, and there was functional improvement (Society for Neuroscience Abstracts 2000;26:860).

Chondroitinase ABC was chosen because of its ability to selectively digest chondroitin sulphate molecules—not heparin sulphate molecules, which are also found at the site of injuries and are known to promote tissue repair. The main limitation of long term enzyme infusion is that it induces an immune response. "We see this enzyme as potentially useful in the acute phase of a brain injury, but it would have to be followed by treatments which work in other ways," explained Dr Fawcett. One option would be to dissolve the sugar with chondroitinase ABC and then add something else that blocks further proteoglycan synthesis. Ultimately, the successful treatment of spinal cord injuries is likely to require a cocktail of enzymes and nerve growth factors.

Turning off a well-known chemical switch may allow severed nerves in adult mammals to regenerate, according to a report in this week'sScience. By jamming the epidermal growth factor (EGF) receptor, the authors blocked harmful signals known to limit repair of damaged axons in the central nervous system. Their finding points to a promising new target for restoring neural function following injury, they say.

Previous research that sought to explain why mammalian axons fail to regenerate in the wounded brain or spinal cord found several inhibitory cues that prevent healing. The culprits include proteins associated with myelin and proteoglycans released by the glial scar that forms after neural injury.

In a search for a signal that might override this chemical blockade, a group led by Zhigang He of Children's Hospital in Boston, Mass. cultured neurons on a myelin substrate. They screened approximately 400 candidate compounds, looking for those that could promote growth in this hostile environment. When exposed to a subset of the molecules, neurons sprouted extensions called neurites, the first step to extending axons. That subset of molecules shared the ability to shut down the EGF receptor. Neurites also grew in the presence of two well-characterized EGF receptor inhibitors, but not a control compound.

"It's surprising finding," said Martin Schwab of the University of Zurich, since activation of the EGF receptor is normally associated with proliferation and growth of cells. Schwab has characterized the signaling pathways of myelin proteins but was not associated with this study. In this case, "the EGF receptor is a bad actor," said Marc Tessier-Lavigne, Senior Vice President for Research at Genentech in South San Francisco, Ca. and a co-author of the paper. "Activation of the receptor is involved in blocking things, not in stimulating growth," he said. "It's an unexpected role for the EGF receptor."

Stephen Strittmatter of Yale University School of Medicine in New Haven, Ct., who first described one of these inhibiting proteins, called Nogo, points out that the connection between Nogo, its receptor and the EGF receptor remains to be worked out. "It is still perhaps a little unclear how the Nogo receptor couples to the EGF receptor and how that coupling is required for inhibition of axon growth," he said.

The authors found that cultured neurons bathed with inhibiting proteoglycans derived from glial scars also grew neurites when the EGF receptor was blocked. That's interesting because proteoglycans and proteins associated with myelin signal through separate biochemical channels, Tessier-Lavigne said. "The EGF receptor seems to be a point of convergence of these two disparate sets of signals," he said.

This common switch could be a potent new target for therapies aimed at repairing damaged nerves. "If with one manipulation – blocking the EGF receptor – you can block the actions of multiple factors, then you can hope to have a bigger effect than if you block any one factor or any one signaling pathway," Tessier-Lavigne told The Scientist.

"The beauty of this observation is that some drugs that will block this pathway have already been approved for the treatment of cancer," said Marie Filbin of Hunter College in New York City, who also works on axon-inhibiting proteins. "If further animal studies prove promising," she said, "the clinical work will move forward very quickly."

Genentech already sells an EGF-receptor-blocking drug called Tarceva, which is approved for the treatment of lung cancer, and plans to begin testing it on a mouse model of spinal cord injury, Tessier-Lavigne said.

Magnetic Therapy and Nerve Regeneration
 
Pulsed magnetic field therapy found effective at regenerating nerve tissue in studies performed since the 1970's.  Dispite being found to be effective and safe, these techniques have never been applied to medical practice due to their simplicity and effectiveness.  Where pulse repetition rate (frequency measured in Hertz) and magnetic flux density (amplitude measured in Gauss or Tesla) are both within certain parameters, pulsed magnetic field research has proven that PEMF's are capable of equal or better results than conventional therapies and invasive procedures without side effects or risk of infection. Pulsed electromagnetic field research has proven routinely that PEMF therapy is capable of inducing substantial healing even where conventional medicine has failed.

Beside promoting various healing mechanisms, pulsed electromagnetic field therapy has been found to have substantially beneficial neuroendocrine, neurological and psychological effects; as well as having ability to promote bone, tissue and nerve regeneration.

BBC NEWS: Tuesday, 11 May, 2004, 09:13 GMT 10:13 UK

Magnetic therapy may help people with spinal cord injuries.

Doctors at Imperial College London administered magnetic stimulation to the brains of people with partial damage to their spinal cord. The therapy led to improved muscle and limb movement, and increased ability to feel sensations.

Details of the technique - known as repetitive transcranial magnetic stimulation (rTMS) - are published in the journal Spinal Cord. It works by using an electromagnet placed on the scalp to generate brief magnetic pulses, about the strength of an MRI scan. These pulses stimulate the part of the brain called the cerebral cortex.

The technique was tested on four patients with what are known as incomplete spinal cord injuries. This is where the spinal cord has not been entirely severed, but the patient has still lost the ability to move or feel properly below the injury point.

Researcher Dr Nick Davey said: "Through rTMS we may be able to help people who have suffered partial injuries to the spinal cord recover some of their movement and feeling. "We think it works by strengthening the information leaving the brain through the undamaged neurons in the spinal cord. It may work like physiotherapy but instead of repeating a physical task, the machine activates the surviving nerves to strengthen their connections."

The patients had all sustained their injuries at least 18 months previously and had already received conventional rehabilitation including physiotherapy. They were all considered stable in that they were no longer undergoing natural improvement. The patients received both real and sham rTMS treatment over a three-week period. The rTMS treatment involved five consecutive days of magnetic stimulation for one hour per day.

The researchers focused on a phenomenon called intracortical inhibition which makes it easier for message from the brain to pass down the spinal cord to the rest of the body. They found rTMS treatment resulted in a 37.5% drop in intracortical inhibition, compared with normal physiotherapy.

This reduction in intracortical inhibition was accompanied by improvement in both motor and sensory function, which lasted for at least three weeks after the treatment. Dr Davey said: "Despite this, we still need to be extremely careful in interpreting these results as we only sampled a small number of patients.

"Further studies on larger groups of patients will need to be carried out before we will know if this treatment is fully effective. "Similarly we have no idea how long the treatment benefits will last over a longer period."

The treatment was originally designed to treat psychiatric disorders, and has been used in treating some of the symptoms of schizophrenia.
 
In short, research is ongoing, some of which can be applied in the present. Those paralyzed today may regain movement in the not too distant future, maybe within the next 5-10 years.In nerve damage, treatment within the first 12-24hrs. is critical for maximal recovery. Those with nerve damage, taking chondrotin sulfate supplements, should either curtail or discontinue their use as these supplements enhance chondroitin sulfate levels in the body and may reduce or eliminate any form of recovery. 


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