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LARGE protein can overcome defects in some types of muscular dystrophy

Muscular dystrophy is a group of genetic diseases characterized by progressive muscle degeneration. Working with mice with a type of the disease, researchers have found that by expressing an enzyme that attaches sugar molecules to a protein essential for proper muscle structure, they can restore normal muscle function.

Interestingly, the scientists found evidence of similar benefits when they expressed the protein, known as LARGE, in cells from patients with similar types of muscular dystrophies with distinct gene defects, suggesting that this approach may have clinical benefits for patients with the debilitating disease.

The study, led by Howard Hughes Medical Institute investigator Kevin P. Campbell at the University of Iowa College of Medicine, was published online in the journal Nature Medicine on June 6, 2004. Campbell's co-authors on the paper were from the University of Iowa, the University of Toronto, Uppsala University in Sweden, and the National Center of Neurology and Psychiatry in Tokyo. The study complements additional work by Campbell and colleagues from the Scripps Research Institute in California, the California Pacific Medical Center Research Institute, and Uppsala University, which elucidated the critical role of LARGE in the processing of a protein required to link muscle cells to their surrounding matrix. This work was published in an advance online publication of Cell on June 3, 2004.

Muscular dystrophy is a group of genetic diseases characterized by progressive muscle degeneration. A subset of muscular dystrophies have recently been linked to mutations in a group of enzymes involved in adding sugars to the muscle protein alpha-dystrogylcan, in a process known as glycosylation. Without the attached sugars, alpha-dystroglycan is unable to carry out its function of linking the internal structural proteins of muscle cells to the surrounding extracellular matrix, providing essential structural support that pro
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
8-Jun-2004


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