PROTEIN STIMULATES MUSCLE REPAIR,
HOLDS POTENTIAL FOR TREATING MUSCULAR DYSTROPHY

TUCSON, Ariz., May 8, 2003 — Researchers funded by the Muscular Dystrophy Association have discovered that a protein called dysferlin plays an essential role in repairing muscle fibers that have been ripped and torn by repeated contraction.

"Once we learn more about this protein and others involved in muscle repair, we may find a way to enhance the repair process so that it's helpful in treating muscular dystrophy," said lead researcher Kevin Campbell, a professor of physiology at the University of Iowa in Iowa City and an investigator of the Howard Hughes Medical Institute.

Muscular dystrophies are a group of genetic diseases that cause muscle weakness and wasting in hundreds of thousands of Americans.

Two rare types of muscular dystrophy, limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM), are caused by a genetic deficiency of dysferlin, which is present in normally functioning muscle. The protein was identified in 1998, but until now its normal role in muscle has been a mystery.

Campbell and his research associate Dimple Bansal probed dysferlin's functions by creating mice with a genetic deficiency of the protein. Their study is the cover article in today's issue of Nature.

Campbell and Bansal examined the muscles of the dysferlin-deficient mice and found signs of muscular dystrophy, including disruptions in the plasma membrane (the surface around muscle fibers and other cells).

Closer examination revealed that dysferlin is needed to patch those disruptions. Previous studies have shown that damaged plasma membranes can be resealed by vesicles (tiny spheres of membrane that home to the site of damage and fuse together to form a patch). The researchers observed an accumulation of such vesicles just inside the plasma membrane in muscle fibers of dysferlin-deficient mice. This is the first evidence for such a patching mechanism in muscle cells, Campbell said.

In collaboration with Paul McNeil from the Medical College of Georgia, Campbell's group performed experiments that showed dysferlin mobilizes to damaged areas of plasma membrane in normal muscle fibers, and that when dysferlin-deficient muscle fibers are punctured with a laser beam, they're slow to seal the disrupted membrane.

In people with LGMD2B and MM, "normal wear-and-tear to muscles caused by contraction is probably not repaired efficiently," Campbell said. "With time, the damage accumulates, and eventually leads to muscle degeneration and weakness."

Dysferlin levels appear to be increased in muscle biopsies from boys with Duchenne muscular dystrophy, he said, suggesting that the muscle is trying to repair itself. To determine whether boosting dysferlin levels can slow Duchenne MD, a much more common form of the disease, he plans to genetically engineer mice with the disease to overproduce dysferlin.

Other proteins related to dysferlin might be used to compensate for its loss in LGMD2B and MM.

MDA is the nonprofit health agency dedicated to curing muscular dystrophy, ALS and related diseases by funding worldwide research. The Association also provides comprehensive health care and support services, advocacy and education.

For more information about MDA's research and services, call (800) 572-1717 or go to www.mda.org.