Patching the Membrane

DMD, BMD, and some forms of LGMD and CMD, may benefit from new finding

by Quest Staff on April 21, 2009 - 2:30pm

Scientists in the United States and Japan say they've identified a previously unknown but crucial step in a natural muscle-cell repair process that could have implications for the treatment of muscular dystrophies, particularly those in which membrane defects are implicated. Those are, for instance, Duchenne MD, Becker MD, some types of limb-girdle MD and some types of congenital MD.

Jianjie Ma of the Robert Wood Johnson Medical School in Piscataway, N.J. (part of the University of Medicine and Dentistry of New Jersey), with Hiroshi Takeshima of the Kyoto (Japan) University Graduate School of Pharmaceutical Sciences, and colleagues, have found that a muscle protein called mitsugumin 53 (MG53) is an essential component of the membrane repair machinery in muscle cells.

The researchers, who published their findings in the January 2009 issue of Nature Cell Biology, say the finding is relevant to both skeletal muscle fibers and cardiac muscle cells.

Muscle-membrane repair, the researchers note, is required in response to exercise, injury, aging and a variety of muscle conditions. They describe a three-part repair process in which: MG53 first senses damage to the membrane; MG53 steers vesicles (bubbles) carrying repair molecules to the damage site and holds them in place; and the vesicles fuse with the membrane, forming a repair patch.

DMD cell diagram
Defects in the muscle-fiber membrane underlie many muscular dystrophies. The discovery of the role of muscle protein mitsugumin 53 (MG53) opens up a possible new therapeutic target.

Several years ago, MDA-supported researchers identified another protein, now called dysferlin, that participates in the membrane repair process. Dysferlin deficiency causes type 2B limb-girdle muscular dystrophy in some patients and a type of distal MD called Miyoshi myopathy in others.

The researchers say future studies are needed to see whether MG53 and dysferlin are part of the same or different repair pathways.

"As MG53 is restricted to the heart and skeletal muscles, its membrane reparative function provides an entirely new paradigm for potential therapy of muscle and cardiovascular diseases, including muscular dystrophy, cardiomyopathy [cardiac muscle degeneration] and age-related muscle wasting," the authors say.

Editor's note: In June 2009, researchers announced that MG53 works in combination with two other proteins, dysferlin and caveolin 3. See Three-Protein Repair Cluster Identified.



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