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In the second area of approach--getting damaged nerves to work again--the researchers' focus is on restoring connections that are intact after an injury but for some reason no longer work. This is where the problem of remyelination comes in. Studies of multiple sclerosis patients have proved useful; MS is an autoimmune disorder in which immune cells strip the spinal-cord nerves of their myelin. Decades ago, MS researchers began testing a derivative of coal tar, 4-aminopyridine (4-AP), to help MS patients gain as much use of their existing nerves as possible. The benefit of 4-AP in paralysis studies came when research with animals showed that a lack of myelin was significant in loss of muscle control. Paralyzed animals given intravenous 4-AP were not necessarily able to walk, but they showed regained muscle reflexes.
Since 1990, about 100 paralyzed patients have been given 4-AP in clinical trials, and about one-third of them have regained some function. Keith Hayes, a neuroscientist at the University of Western Ontario in London, Canada, who has been involved in the trials, says, "We have seen improvements in sensation and motor function, reduced spasticity and reduced pain, and improvement in bowel, bladder and sexual functions." MS researchers may come up with yet another useful therapy for spinal-cord injuries. At the Mayo Clinic in Rochester, Minnesota, Dr. Moses Rodriguez is testing the use of antibodies as catalysts for the making of myelin in MS patients. Antibodies with a low affinity for myelin-producing cells in the central nervous system may stimulate these cells to divide and develop. Thus, Rodriguez argues, paralysis patients may prompt their own bodies to produce the myelin their axons need.
Of course, it is the third area of approach, the regeneration of cells, that gets researchers and patients most excited. Young remains both cautious and optimistic: "When you're tinkering with the growth of things in the central nervous system, you're playing with the very nature of the beast," he says. "It may take four to five years before a regenerative therapy goes to clinical trial."
Until the mid-1980s, researchers assumed that nerves in the central system were simply incapable of regrowth once they were damaged. A researcher at McGill University in Montreal, Alberto Aguayo, turned this assumption around by demonstrating that a nerve taken from an animal's leg and grafted onto the central nervous system allowed the nerve cells to grow along the transplanted nerve. Evidently there was nothing wrong with spinal-cord nerves, but something in the central nervous system was impeding their growth.
Since then, scientists have refocused their attention on nerve-growth factors, first identified in 1951 by Rita Levi-Montalcini of Washington University in St. Louis, who studied neural development in chick embryos. The ngf protein is present in the peripheral nervous system, but cells in the central system do not normally respond to it. Researchers are investigating ways to use ngf and proteins like it to encourage new axonal growth from the spinal cord. ngf injected into the spinal cords of rats revived connections from the spinal cord to the brain, but it remains uncertain whether more or less ngf is better for nerve growth.