Meanwhile, in the Lab...

Rem

arkable as Christopher Reeve's rehabilitation has been, doctors know that physical therapy can go only so far. To cure paralysis, they will have to find a way to repair or replace damaged spinal-cord nerves. Most of the research to date has been conducted on laboratory animals, but those experiments have set the stage for what scientists believe could be a burst of advances in human patients. "This is an exciting time in spinal-cord-injury research," says Dr. Wise Young, director of the Center for Collaborative Neuroscience at Rutgers University. "The progress in getting experimental therapies into clinical trials is astounding."

Like a strand of tightly woven twine, the spinal cord is actually made up of thousands of nerve fibers that are strongest and most effective when they work as an intact unit. Even the slightest fraying of the cord can interrupt or weaken signals traveling from the brain to the muscles, in some cases resulting in paralysis. To bridge these gaps in the tapestry of nerve cells, you have to either coax existing neurons to grow across the neural divide or introduce new cells to replace the damaged ones. Often the two strategies feed off each other: the growth of existing neurons stimulates the sprouting of new nerve cells, and those actively developing cells provide older ones with the right cellular environment to jump-start their own growth.

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One of the most promising new therapies is a compound called Fampridine-SR (4-AP), now beginning final phases of testing in human patients. If okayed by the Food and Drug Administration, 4-AP will become the first available treatment that can actually restore function in those with spinal-cord injuries; as many as 30% of test subjects who have taken the nerve enhancer have experienced improved movement and feeling in their limbs. Meanwhile, dozens of other compounds, including various nerve-growth factors, have restored muscle activity in paralyzed animals.

Nondrug strategies, especially electrical stimulation of spinal-cord nerves, are also raising hopes. Work in dogs injured in accidents has shown that an alternating electric current applied directly to a damaged spinal cord can restore movement in the legs if administered in the first two weeks after injury. Scientists speculate that the current helps one type of nerve cell line up along the spine, creating a template that can guide other neurons across gaps in the cord.

Lagging behind these efforts are treatments involving stem cells. Some researchers believe these highly versatile cells may eventually provide the cornerstone of all future spinal-cord treatment. Luckily, given the political controversy surrounding embryonic stem cells, it seems that stem cells extracted from adults are just as capable of developing into spinal-cord nerves as those taken from embryos.

Already, scientists in Australia, Portugal and China have removed a group of stem cells involved in the sense of smell from regions deep in the brain and transplanted them into a small number of patients with spinal-cord injuries. These cells are constantly regenerated, making them a potentially rich source of new cells that might be coaxed into becoming spinal-cord neurons. Several teams in the U.S. are investigating another group of stem cells taken from the nasal cavity, where they are much easier to harvest.

"There is a lot more research on spinal-cord injury today than 10 or 15 years ago," says Dr. Fred Roisen of the University of Louisville, one of the researchers involved in the nasal-stem-cell studies. "The future holds a lot of promise." It's worth remembering, however, that progress on any of these fronts will come slowly and, like Reeve's physical therapy, one step at a time.