Bench discovery raises hopes for therapy in spinal cord injuries

Scientists can regrow severed brain and spinal cord axons in the laboratory, but something in the adult central nervous system prevents their regeneration in humans. As a result, paralysis and other disabilities resulting from brain or spinal cord trauma are irreversible in most cases. Three separate research teams, including a group from Yale and Harvard, have identified a gene and its protein that appear to block axon regeneration. The discovery of what is termed “Nogo” raises the possibility of developing a therapeutic means of inhibiting its activity, increasing the hopes that brain and spinal cord injuries might one day be reversible.

Previous experiments have shown that the natural adult brain environment contains one or more substances that inhibit the regrowth of central nervous system axons, unlike nerve cell connections in other parts of the body. Three papers published in the January 27 issue of Nature, including the Yale-Harvard group’s, reported the cloning of Nogo and identified its activity as an inhibitor present in the brain and very likely responsible, at least in part, for the failure of axons to regenerate.

The Yale-Harvard study showed that the Nogo protein, by itself, stops axon growth in laboratory conditions. The protein is found only in those areas of the brain which are most hostile to axon growth.

“Is this the answer?” asks Stephen M. Strittmatter, M.D., Ph.D., associate professor of neurology and of neurobiology, leader of the Yale team. “We’re pursuing experiments that will take things to the next step.” These include generating a mouse model in which the Nogo gene will be “knocked out” or disabled, and then inducing central-nervous-system injuries to see if axons regenerate. The Yale members of the group also are trying to develop a possible blocker for the action of Nogo and to identify the receptors mediating its activity.