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A BLUEPRINT FOR REBUILDING BROKEN SPINAL CORDS

Ever since the days of the Egyptians, doctors have believed that injuries to the spinal cord and other parts of the central nervous system were beyond medicine's reach. For virtually all paralysis victims, the message was bleak: Don't even hope for recovery. ''When I got out of medical school in 1981, the dogma was the same as it has been for 1,000 years. If you make a cut in the spinal cord or brain, it can't grow back,'' explains Dr. Ron Cohen, president of New York biotech startup Acorda Therapeutics. ''It's been a field that for thousands of years has been completely refractory to medical intervention.''

Until now. Using a whole series of bold new approaches, scientists have been able to do everything from fixing spinal-cord injuries in rats to slowing brain degeneration in Parkinson's disease. ''It's a complete revolution in the field,'' says Cohen. ''Everyone now believes that we will have restorative therapies in clinical trials in the next two to three years.''

For a glimpse of this new world of nerve regeneration, drop by the lab of Dr. Mark H. Tuszynski at the University of California, San Diego. Tuszynski's team has been able to genetically engineer cells to make substances that promote nerve growth. The researchers then can inject these gene-altered cells into the damaged spinal cords of rats. The results are little short of amazing. Tuszynski has been able to make paralyzed rats walk again -- albeit not perfectly. And he envisions more sophisticated approaches in which added genes can be turned on and off at the right time to significantly boost the effectiveness of the therapy.

REGROWABLE. Tuszynski's success at delivering nerve growth factors is only one of many exciting developments in the field. Another tack builds on a key discovery by Swiss scientist Martin Schwab in 1988. Researchers used to think that the nerves in your hand are fundamentally different from those in the brain and central nervous system (CNS). Nerves in your hand (part of the so-called peripheral nervous system) are able to grow back after injury, although slowly. But nerve cells in the brain and CNS, doctors believed, no longer have that ability.

What Schwab found was that the CNS hasn't really lost the ability to regrow. Instead, regrowth is blocked by powerful inhibitory substances. Schwab was able to isolate two such substances. Since then, he has devised ways of blocking their action. One method involves a so-called monoclonal antibody that binds to the inhibitors and neutralizes them. In a recent paper in Nature Neuroscience, Schwab's team described how they damaged one side of the base of the brain in rats. Rats so injured lose the ability to move and control one of their front paws. But after treatment with the monoclonal antibody, the rats undergo a remarkable recovery, regaining much of the lost ability.

DELAYED REACTION? Of course, there's a vast difference between regenerating nerves in rats and helping human victims of paralysis toss aside their wheelchairs and walk again. Schwab's results are ''exciting, but it's still early-stage research,'' cautions Murray A. Goldberg, CFO of Regeneron Pharmaceuticals Inc., a Tarrytown (N.Y.), biotech company that owns the rights to Schwab's monoclonal antibody. One looming question, for instance, is how long injured nerves retain the ability to regrow or regenerate. In the animal studies to date, scientists treat the animals soon after the damage is done. But what about the tens of thousands of people who have been paralyzed for years? Can the growth potential of their nerves be reawakened?

No one knows yet. ''That's been one of the major criticisms of the field,'' admits Dr. Wise Young, a neuroscientist and nerve regeneration pioneer at Rutgers University. ''No one has done an experiment months or years after injury.''

But such experiments are likely soon. Already, at least a half-dozen different approaches to regenerating nerves have shown promise in animals. In the next few years, researchers want to find out which of these, either alone or together, offers the most hope for people. ''The task now is to find the best combination and optimize it so we can take it to clinical trials,'' explains Young. And if it works, as many scientists believe it will, medicine will finally be able to offer real treatment instead of simply confirming a life sentence of paralysis.

By John Carey in Washington



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