Hope sustains center’s research on paralysis

When Stephen G. Waxman, M.D., Ph.D., moved from Stanford’s School of Medicine to Yale in 1986, he didn’t pack light: he brought with him several scientists, including Jeffery D. Kocsis, Ph.D., and Joel A. Black, Ph.D., and a million dollars’ worth of equipment.

On arrival, Waxman, now the Bridget Marie Flaherty Professor of Neurology, Neurobiology and Pharmacology, set up shop on the campus of the VA Connecticut Healthcare System in West Haven, Conn., where, with financial backing from groups of paralyzed veterans, including the Paralyzed Veterans of America (PVA), he established the Center for Neuroscience and Regeneration Research (CNRR).

Scientists at the CNRR, which marked its 20th anniversary last October with the opening of a new $3.8 million wing, are doing some of the foremost research on restoring function after spinal cord or brain injury. There, Waxman, CNRR director and longtime chair of the medical school’s Department of Neurology, and associate directors Kocsis and Black lead a staff of thirty-odd Yale physiologists, pharmacologists and stem cell biologists working on cellular repair of the spinal cord and brain using transplanted cells and stem cells; molecular repair of demyelinated cells in disorders such as multiple sclerosis (MS); and understanding the basis of neuropathic pain, or long-term pain experienced after injury to the nervous system (or, in some cases, when there is no injury at all).

While scientifically diverse, the center’s investigators are united by a common desire to reduce patients’ discomfort and restore function to paralyzed limbs. “We know from earlier experiments that if we can coax just 15 percent of the axons in the motor tract of the injured spinal cord to conduct impulses, it will restore gait,” Waxman says. “We won’t be making somebody into a ballet dancer, but imagine telling somebody who’s confined to a wheelchair that they could take ten labored steps—enough to get from their wheelchair into a car. Or giving somebody who has no function below the shoulders just enough function in their spinal cord so they can grasp and use a pencil.”

The key to realizing such hopes for people like the 100 wheelchair-bound veterans who arrived to fete the CNRR’s 20th year, Waxman says, is continued research. His group has found, for instance, that remissions occur in MS without the production of new myelin, an insulating sheath that coats nerve cell axons and is vital for the conduction of nervous signals in the brain and spinal cord. “We know axons can rebuild themselves in disorders like MS, and we know they produce new sodium channels, which act as batteries within their membranes so they can convey information, even though they have lost their myelin insulation,” Waxman says. “Now, we want to be able to turn that process on and off at will.”

While myelin may not always be necessary for improvements in nerve conduction, remyelination certainly does help. Kocsis’s group is interested in remyelination therapies for spinal cord repair based on adult stem cells derived from bone marrow. Kocsis, professor of neurology and neurobiology, has found that such cells do not need to be implanted directly into the brain or other injured sites, but can be delivered intravenously and still lead to the production of new myelin and improved condition. In cases of non-penetrating, or closed, spinal cord injury, often caused by motor vehicle accidents or athletic mishaps, Waxman says, “It used to be thought they had cut the cord across. They usually haven’t. Axons run up and down through the lesion in continuity, but they don’t conduct because they’ve lost their myelin insulation. And we view that as a target of opportunity.”

Will victims of paralysis someday be able to regain function? “You need luck as well as everything else,” Waxman says. “If I was sure that a particular path would get you there, we would do it and get there. So we are taking multiple, parallel approaches. But I think that with hard work and a bit of luck, we may well get there.”