Enzyme Blocks Duchenne MD in Mice

TUCSON, Ariz., April 15, 2002 — Although sugars rarely occupy the limelight in medical research, scientists funded by the Muscular Dystrophy Association have found that a sugar-adding enzyme could one day be used to treat Duchenne muscular dystrophy (DMD).

In today's issue of the Proceedings of the National Academy of Sciences, Paul Martin and his colleagues at the University of California in San Diego report that increased levels of the enzyme CT GalNac transferase can block muscle wasting in mice with DMD.

"In terms of therapy for DMD, this [enzyme] is a new target to look at that was previously not evident to anybody," Martin said.

MDA Director of Research Development Sharon Hesterlee said, "These results add to our growing understanding of the biology of this disease and add a new approach to our arsenal of potential therapies."

DMD — the most common and deadly childhood form of muscular dystrophy — almost exclusively affects boys. Most lose the ability to walk in their early teens, and succumb to respiratory or cardiac failure in their 20s.

The dystrophin protein is part of an essential complex of proteins in the membrane (surface) of muscle fibers. In DMD, the absence of dystrophin makes that complex fall apart, except in small patches of membrane that contain the dystrophin-like protein utrophin. Many scientists hope to treat DMD by supplying dystrophin or extra utrophin.

But Martin and his colleagues noticed that CT GalNac transferase, an enzyme that attaches a small sugar group onto proteins, was concentrated around utrophin complexes. Guessing that the enzyme might help stabilize utrophin complexes, they introduced extra copies of the gene for the enzyme into mice with DMD.

In those mice, the enzyme and the utrophin complexes spread over the entire surface of each muscle fiber, and kept the fibers from degenerating.

In people, the enzyme could be delivered via gene therapy or activated by a drug, Martin said. Similar strategies are being pursued with dystrophin and utrophin, but the enzyme might be superior because just a little of it could have far-reaching effects, he said.

MDA is a voluntary health agency working to defeat more than 40 neuromuscular diseases.