Spotlight on Research for 2004

August 2004 (historical)

Protein May Hold Key to Repair of Damaged Muscles

For people with muscular dystrophies, a group of genetic diseases characterized by progressive weakness and degeneration of the muscles, treatment is usually limited to physical therapy to prevent painful muscle contractures, orthopaedic appliances for support and orthopaedic surgery to help correct some of the problems caused by the disease. But thanks to new research findings by scientists at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and their colleagues, there may one day be a better option: treatments to promote the regeneration of damaged muscles.

These treatments, the researchers say, could be based on a protein called follistatin, which they have discovered plays a critical role in the growth and regeneration of adult skeletal muscle cells, and/or a group of chemicals called histone deacetylase (HDAC) inhibitors that help follistatin do its job.

Vittorio Sartorelli, M.D., from the Laboratory of Muscle Biology at the NIAMS, along with colleagues at the Salk Institute and Rome's Dulbecca Telethon Institute, have found that the level of follistatin is significantly elevated in muscle cells when they are treated with HDAC inhibitors. HDAC inhibitors stimulate the formation of mature muscle cells from immature precursor cells. When follistatin levels are reduced, however, HDAC inhibitors no longer stimulate adult muscle growth, the researchers found. The regeneration activities of the HDAC inhibitors appear to function only in skeletal muscle, since follistatin is not stimulated in other cells tested. In animal studies, administering an HDAC inhibitor produced signs of muscle regeneration in regions of injured skeletal muscle tissue.

Follistatin is known to be important to reproduction and embryonic development; however, Dr. Sartorelli says the new study establishes for the first time that follistatin promotes the recruitment and fusion of immature muscle cells to pre-existing adult muscle fibers.

"These findings suggest that follistatin is a promising target for future drug development of muscle regeneration. HDAC inhibitors, by stimulating, follistatin, could be pharmacologically useful as stimulants of muscle regeneration," Dr. Sartorelli says.

The researchers are currently investigating whether these inhibitors might be a viable treatment to regenerate healthy new muscle tissues in animal models of muscular dystrophies, he says. Much more work must be done, however, before this research could be applied to human disease.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information Clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at

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Iezzi S, et al. Deacetylase inhibitors increase muscle cell size by promoting myoblast recruitment and fusion through induction of follistatin. Developmental Cell 2004;6(5):673-684