May 29, 2002
NEW YORK (Reuters Health)
A synthetic peptide, NEP1-40, that acts as a competitive antagonist of the Nogo myelin-derived axon outgrowth inhibitor receptor has been developed by Connecticut-based researchers. They found that NEP1-40 treatment of rats after spinal cord injury (SCI) results in axonal growth and significant functional recovery.
"A therapeutic agent with similar action might be developed for humans that would promote nerve fiber growth after SCI, head trauma, or stroke," Dr. Stephen M. Strittmatter told Reuters Health.
Dr. Strittmatter and associates, of the Yale University School of Medicine in New Haven, found that NEP1-40 (Nogo extracellular peptide, residues 1-40) prevents the growth cone collapse of chick dorsal root ganglion cultures associated with Nogo-66 receptor agonists.
They administered NEP1-40 or its vehicle intrathecally to rats, at the site of a mid-thoracic dorsal hemisection injury, daily for 4 weeks. After vehicle treatment, they found that the dorsal corticospinal tract (CST) ended abruptly at the site of the transection Below the lesion, only fibers associated with uninjured ventral CST were observed.
In NEP1-40 treated rats, however, axonal sprouting adjacent to the dorsal CST was increased more than 10-fold, the investigators report in the May 30th issue of Nature. Longitudinal sections demonstrated "a plexus of convoluted fibers crosses from the rostral to caudal cord," they write. At distances of 11 to 15 mm caudal to the lesion, they observed 20 to 30 CST fibers in NEP1-40 treated animals, versus zero to two in vehicle-treated rats.
The sprouting response was observed only in the cut axons, not in the CST of uninjured rats or uninjured ventral CST of hemisected rats treated with NEP1-40. Both corticospinal and raphespinal axons were regenerated, the Yale team noted. By 14 days after SCI, NEP1-40 treatment resulted in significantly higher locomotion scores, an improvement that persisted through day 28.
Dr. Strittmatter noted that, before human studies can be initiated, the Nogo blocker needs to be refined and evaluated for potentially harmful side effects. The goal is to maximize the potency, effectiveness, and stability of the compound, he said. Dr. Strittmatter and his associates will also examine the efficacy of the compound at different time points after injury.
© 2002 Reuters Ltd