From; Roberta Friedman, Ph.D., ALSA Research Department Information Coordinator

The ALS Association (ALSA) announced continued funding to Stephen Strittmatter, M.D., Ph.D., of Yale University in New Haven, Connecticut, to support an ongoing effort to understand the factors that prevent damaged nerve fibers from growing back.

Strittmatter been investigating the role of the inhibitor proteins called Nogo, and their receptor, in ALS. Since drugs that affect the Nogo family exist, if Nogo proves to be a player in ALS, a new therapeutic strategy could rapidly be developed.

“It is already clear that therapeutics directed at Nogo and the Nogo receptor can result in the re-growth and repair of nerve fibers when they have been cut by trauma in animals,” Strittmatter said. “Since one of the earliest changes in ALS is the degeneration of nerve fibers, stimulating their re-growth may provide a novel therapeutic approach in ALS."

An expert on the Nogo proteins and their receptors, Strittmatter has available mice that lack the receptor, and mice that lack certain Nogo proteins. He can breed these mice with mice that have the mutant protein, copper-zinc superoxide dismutase (SOD1) linked with some inherited forms of ALS. In this way, the effect of the Nogo family on ALS can be examined.

Nogo is a family of proteins, some of many components of the insulating myelin in the central nervous system that helps nerves function efficiently. As animals develop, the myelin wraps around growing nerve fibers and helps to keep nerve tracts together and headed towards their proper targets. But in adults, Nogo and other so-called myelin inhibitors prevent damaged nerve fibers from growing back through the myelin of existing nerve tracts.

In the new experiments planned, Strittmatter and collaborators will find out if implants of embryonic stem cell derived neurons will be able to send their axons farther when the implanted mice lack Nogo or when the transplanted cells lack Nogo receptor. He will also verify that one of the Nogo proteins has a protective effect in motor neurons, and what might be its action on axon transport, the means by which nerve cells move needed materials and keep themselves healthy