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Treatment stimulates growth and regeneration of injured adult skeletal muscle

Cell Press

Scientists have discovered that a group of chemicals known as Histone Deacetylase (HDAC) inhibitors stimulate growth and regeneration of adult skeletal muscle cells by increasing expression of the protein follistatin. The research, published in the May issue of Developmental Cell, may provide new avenues for developing effective means to promote regeneration in muscular dystrophies.

Dr. Vittorio Sartorelli from the Muscle Gene Expression Group in the Laboratory of Muscle Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, in Bethesda, Maryland, and colleagues at the Salk Institute and the Dulbecco Telethon Institute in Rome report that HDAC inhibitors, which stimulate the formation of mature muscle cells from immature precursor cells, also cause a significant elevation of follistatin levels. When follistatin levels are reduced, then HDAC inhibitors no longer stimulate adult muscle growth. The regeneration activities of the HDAC inhibitors appear to function only in skeletal muscle, since follistatin is not stimulated in other cell types tested. In animal studies, administration of an HDAC inhibitor produced clear signs of muscle regeneration in regions of injured skeletal muscle tissues.

"Our findings establish for the first time that follistatin promotes the recruitment and fusion of immature muscle cells to pre-existing adult muscle fibers. These results suggest that follistatin is a promising target for future drug development of muscle regeneration. HDAC inhibitors, by stimulating follistatin, could well be pharmacologically useful as stimulants of muscle regeneration. We are investigating whether these inhibitors are a viable treatment to regenerate healthy new muscle tissues in animal models of muscular dystrophies," explains Dr. Sartorelli. The functional link between HDAC inhibitors, follistatin, and adult muscle regeneration is especially provocative as an HDAC inhibitor is already being used clinically in humans as an anti-cancer therapeutic.

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Simona Iezzi, Monica Di Padova, Carlo Serra, Giuseppina Caretti, Cristiano Simone, Eric Maklan, Giulia Minetti, Po Zhao, Eric P. Hoffman, Pier Lorenzo Puri, and Vittorio Sartorelli: "Deacetylase Inhibitors Increase Muscle Cell Size by Promoting Myoblast Recruitment and Fusion through Induction of Follistatin"

Publishing in Developmental Cell, Volume 6, Number 5, May 2004.

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