U. Iowa muscular dystrophy discovery may lead to new treatment approaches

Expressing high levels of a sugar-adding protein known as LARGE in mice that lack the protein can prevent muscular dystrophy in these animals, according to studies by researchers at the University of Iowa Roy J. and Lucille A. Carver College of Medicine. Furthermore, the research suggests that LARGE protein also can restore normal function to a critical muscle protein that is disrupted by glycosylation (sugar-adding) defects in several different human muscular dystrophies.

The team's findings, which appear June 6 in an advanced online publication of Nature Medicine and online in the journal Cell on June 3, might lead to new treatments for this particular class of muscular dystrophies and other muscle diseases caused by glycosylation defects.

A group of muscular dystrophies, which include Fukuyama Congenital Muscular Dystrophy, Walker-Warburg Syndrome and Muscle-Eye-Brain disease, are caused by mutations in glycosylation enzymes proteins that add sugars to other proteins. In these diseases, defects in the sugar-adding mechanism disrupt the properties of alpha-dystroglycan, a protein critical for normal muscle function.

Previous work by the UI researchers led by Kevin Campbell, Ph.D., the Roy J. Carver Chair of Physiology and Biophysics and interim head of the department, professor of neurology, and a Howard Hughes Medical Institute (HHMI) Investigator, showed that abnormal glycosylation disrupts alpha-dystroglycan's ability to interact with other proteins and leads to muscle degeneration and brain defects in these muscular dystrophies.

LARGE protein is mutated in patients with congenital muscular dystrophy 1D. In the Nature Medicine article, Campbell and his colleagues examined the effect of restoring expression of LARGE in mice that lacked the protein and found that gene transfer of the protein into this animal model of the disease prevented the development of muscular dystrophy.

More surprisingly, the research team also

Contact: Jennifer Brown
University of Iowa

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