Gene Identified in Spinal Cord Injuries
by
Jeff Barnard,
Associated Press Writer

5:41 PM EST, January 26, 2000; Scientists have identified a gene that prevents the brain and spinal cord from rewiring themselves after an injury, pointing the way to new treatments that might someday help paralyzed "Superman" star Christopher Reeve and 250,000 Americans like him. Dubbed "Nogo" because of its inhibiting effect, the gene produces a protein that prevents nerve-cell connections in the central nervous system from regenerating after they are cut. Experiments in rats showed that when the protein is blocked, the spinal cord can repair itself.

Neurologists hailed the work as a landmark step. But they cautioned that other factors may also inhibit nerve regrowth. "It is important not to give patients false hope," said Dr. Ben Barres, a professor of neurology at Stanford University. "But I think there are a lot of grounds for optimism now."

The findings were reported in Thursday's issue of the journal Nature by scientists in Switzerland, England and the United States. If the scientists are right, they have solved an old mystery: Why can't connections in the central nervous system -- the brain and spinal cord -- repair themselves, when connections in the peripheral nervous system -- everything else -- can? The answer is that the Nogo protein is present in the central nervous system but not in the other nerves. Nogo may exist to hardwire the brain and spinal cord -- or fix them in place -- after they have developed, and prevent them from going wild.

A team led by Martin Schwab of the Brain Research Institute at the University of Zurich in Switzerland has been working on Nogo for 15 years, and created an antibody that blocks the Nogo-created protein. In test-tube experiments, nerves dissected from rats were exposed to the antibody. The nerves regrew several hundred nerve connections known as axons, or the tiny branches that transmit impulses from one nerve cell to the next, Schwab reported.

In an additional set of experiments that were not published in Nature, Schwab's team said it partially cut the spinal cords of rats, paralyzing the animals, then gave the rodents the antibody for two weeks. The nerves regrew, and the animals resumed normal activities such as grabbing food pellets and climbing a rope. "We see these animals' recovery functionally," said Isabel Klusman, a medical biologist who works with Schwab. Researchers said the Nogo research may lead to a three-pronged therapy involving a Nogo blocker, some agent to boost nerve growth, and some kind of cell transplant.

Schwab's team never identified the actual gene. That was done by two separate teams, one at the pharmaceutical company SmithKline Beecham in England, the other led by Dr. Stephen Strittmatter at Yale University. Some 11,000 people injure their spinal cords each year, primarily in car wrecks, as football star Derrick Thomas did last Sunday. Reeve has been paralyzed from the neck down, using a respirator to help him breathe, since a 1995 fall from a horse.

Researchers are more cautious than Reeve, but the actor, whose foundation helped finance some of the Nogo research at Yale, said the discoveries are part of a growing body of advances that he believes will allow him to walk again someday. Reeve said he hopes to take part in human tests by Schwab in about five years, once work has progressed to the point he would feel safe. "It will be a question of money and time," Reeve said from his office in Bedford, N.Y. "But the field now is very alive and there is suddenly a lot of progress being made."