February 2004

7 Hot Projects

Continued from page 2

By Erika Jonietz

Spinal-cord trauma treatment
Company: Biogen
Status: Human trials anticipated within three or four years

Biologists have long known that peripheral nerves (such as those in the hands and feet) sometimes grow back after they're injured but that nerves in the spinal cord and brain do not. Now researchers are looking for a way to overcome natural inhibitions to nerve growth and help patients who have suffered spinal-cord trauma or stroke.

In the late 1990s, Yale University neurobiologist Stephen M. Strittmatter isolated a protein in the nerve cells' protective sheath that inhibits the capacity of brain and spinal-cord nerves to regenerate. Strittmatter also identified the molecule on the nerves to which this regrowth-inhibiting protein, called Nogo, binds. Since 2001, Strittmatter has been working with Biogen to find a way to block this receptor and thus allow the nerves to regrow. They have come up with several potential protein drugs, which could be injected into the spinal cord up to a week after injury and would compete with Nogo to bind to its receptor. "The challenge now is to find the best candidate molecule," says Katherine Turner, Biogen's vice president of validation biology.

In early tests on mice and rats with spinal-cord injuries, the approach at least partially reversed paralysis. Despite these encouraging results, however, Turner cautions that most researchers don't consider mice good models for human neurological trauma. Also, it turns out there are two other proteins that bind to the receptor, and it is not yet clear whether the Nogo blockers will displace them as well-a process that may be necessary to trigger regeneration in the human spinal cord.

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