Defect in Protein Glycosylation Linked to Muscular Dystrophy

Researchers have found that a mutation in the gene that encodes the glycosyltransferase called LARGE is present in diseases similar to muscular dystrophy, and by genetically engineering overexpression of the normal gene, it is possible to restore normal muscle cell function.

Investigators at the University of Iowa (Iowa City, USA) worked with a mouse model that lacked the gene for LARGE. Failure of proper transfer of sugar molecules to the muscle cell protein alpha-dystroglycan caused these animals to display symptoms similar to muscular dystrophy in humans.

When the gene for LARGE was transferred into these animals, normal protein glycosylation was restored and symptoms disappeared. These findings and other observations about LARGE were reported in the June 3, 2004, online edition of Cell and the June 6, 2004, online edition of Nature Medicine.

Senior author Dr. Kevin Campbell, professor of neurology at the University of Iowa, said, "The finding that LARGE can restore alpha-dystroglycan function regardless of the type of glycosylation defect is incredibly exciting. This result may have potential application in the development of therapies for an entire group of muscle diseases.”