ORLANDO, Fla., April 8 -- Researchers at Johns Hopkins School of Medicine have identified a set of compounds that appear to overcome an important barrier to regenerating damaged nerves. Their findings could lead to new treatments for spinal cord injury, multiple sclerosis and other neurological conditions.
Targeting a newly discovered mechanism that inhibits the growth of damaged nerves, the researchers found that these compounds caused dissected rat nerves to regenerate under controlled laboratory conditions. Findings were described today at the 223rd national meeting of the American Chemical Society, the world's largest scientific society.
The results add to a growing body of evidence that repairing spinal cord injury -- once thought impossible -- may one day occur, says Ronald L. Schnaar, Ph.D., a professor in the Department of Pharmacology at the university, located in Baltimore, Md., and lead investigator in the study.
"We are getting at the mechanisms that underlie one of the problems in nerve regrowth, but there are others," says Schnaar. "There's no one answer. There is no magic formula for spinal cord repair." Animal studies testing the nerve-regenerating chemicals began recently, he adds.
Nerves consist of axons, long extensions that carry electrical signals. Axons are wrapped by an insulation called myelin, which is essential for normal electrical conduction. When nerve cells are damaged, as in spinal cord injury, myelin sends signals that stop the axons from regenerating.
Schnaar and his colleagues found that molecules called "MAG" (myelin associated glycoprotein) on the myelin send inhibitory signals to complementary molecules called gangliosides on the surface of nerve cell axons. While the MAG-ganglioside interactions are normally stable, MAG binds to and clusters the gangliosides together during nerve injury. It is this clustering of the gangliosides on the nerve cell surface that is thought to inhibit nerve growth, they believe.
While MAG inhibition has been known for some time, Schnaar's lab is the first to identify gangliosides as the nerve cell targets for this inhibition. In the current study, the researchers focused on ways to unlock this inhibition in order to restore nerve growth.
They identified four chemicals -- including antibodies and enzymes known to interfere with myelin-axon interactions -- that induced nerve regeneration in rat brain cells under controlled laboratory conditions, according to Schnaar. He is now testing the nerve-regenerating factors in animal models with damaged nerves to determine if these therapies can work in living systems. Preliminary results are not yet available, he says.
"In the [human] body, nerve damage is much more complicated than our laboratory conditions, and this new knowledge, by itself, is unlikely to solve the problem of nerve regeneration," cautions Schnaar. "However, it is our hope that our discoveries, along with other new discoveries on the molecular basis for nerve regeneration, will help in the search for therapies to improve functional recovery after nervous system injury or disease."
About 11,000 new cases of spinal cord injury occur in this country each year. While there is no cure for paralysis, there are a number of treatment options for nervous system disease and injury, including drugs, cell transplants, artificial nerves and rehabilitation therapy.
The National Institutes of Health, the National Multiple Sclerosis Society and the Stollof Family Fund provided funding for this study.
-- Mark T. Sampson
The paper on this research, CARB 41, will be presented at 4:25 p.m., Monday, April 8, at Convention Center, Room 314A, Level Three, during the symposium, "Multivalent Carbohydrate-Protein Interactions."
Ronald L. Schnaar, Ph.D., is a professor in the departments of pharmacology and neuroscience at the Johns Hopkins School of Medicine in Baltimore, Md.