January 2001

From Yale University

Yale researcher finds new clue to what blocks nerve fibers from regrowing following spinal cord injury or disease

New Haven, Conn. – Researchers are one step closer to reversing brain and spinal cord injuries with the discovery of another molecule in a pathway that prevents axon regeneration, a Yale researcher says.

Stephen Strittmatter, M.D., who holds the Vincent Coates Chair of neurology, as well as associate professor of neurology and neurobiology at Yale School of Medicine, said he and his collaborators have now identified the receptor responsible for inhibiting the growth of injured nerve fibers in the brain and spinal cord by the protein, Nogo.

The finding could lead to the reversal of functional deficits in brain and spinal cord injuries caused by trauma and stroke, or brought about by degenerative diseases, such as multiple sclerosis.

"We had the key and now we have the lock," said Strittmatter, whose study was published this week in the journal Nature. "The importance of the discovery is that by having both the ligand and the receptor molecules in hand, it greatly simplifies the search for inhibitors of that interaction and for therapeutic possibilities."

Strittmatter and his collaborators a year ago published a study identifying the Nogo protein as one important and selective blocker of axon regeneration in the brain after central nervous system injury. Axons are the telephone lines of the nervous system, carrying a nerve impulse to a target cell.

"Once we had Nogo in hand, we needed to know: How does it function? How does it inhibit axon growth? We needed to identify the molecular mechanism of Nogo action," he said.

What the researchers found is a receptor on the axons to which the Nogo protein binds. It is this receptor, Strittmatter said, that inhibits the axon’s regenerative growth.

"The current identification of a receptor mediating Nogo-66 action should greatly facilitate the development of agents with pharmaceutical potential in a diverse group of neurological conditions, such as spinal cord injury, brain trauma, stroke affecting white matter, and chronic, progressive multiple sclerosis," he said.

Collaborators on the study were Alyson Fournier, postdoctoral research fellow, and Tadzia GrandPre, graduate student.











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