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Scientists show drug can counteract muscular dystrophy in mice

Scientists at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other institutions have demonstrated for the first time that a single drug can rebuild damaged muscle in two strains of mice that develop diseases comparable to two human forms of muscular dystrophy. This advance, which is reported online in Nature Medicine, is the latest from a research collaboration that began several years ago by the teams of Vittorio Sartorelli, M.D., at NIAMS and Pier Lorenzo Puri, M.D., Ph.D., now at Dulbecco Telethon Institute (DTI) in Rome, Italy and The Burnham Institute in La Jolla, Calif.

The scientists tested trichostatin A (TSA), an inhibitor of the enzyme deacetylase, in two mouse models of muscular dystrophy (MD): one that naturally develops a disease similar to Duchenne muscular dystrophy in humans, the other genetically altered to develop a form of dystrophy similar to the human limb-girdle muscular dystrophy. At 45 to 90 days of age, the muscles of the MD mice showed much fibrous tissue and infiltration of inflammatory cells. Unlike healthy mice, the mice with MD were unable to either run on a treadmill or swim. MD mice given TSA daily for two to three months, however, were virtually indistinguishable from healthy mice, and biophysical studies showed virtually no difference between the muscle strength of the mice with MD given the deacetylase inhibitor and healthy mice.

"This is the first example of using a drug to counteract muscular dystrophy in mouse models," says Dr. Sartorelli. Yet he points out that the drug is only promoting muscle regeneration it is not curing the defect that causes muscle deterioration. Further studies are needed to determine how long the drug works and if it works in larger animals with bigger muscles, such as dogs, before such drugs can be tested in people.

The finding has its roots in several of the group's earlier advances, the first of which was reported in 2002 in th
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Contact: Ray Fleming
flemingr@mail.nih.gov
301-496-8190
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
4-Oct-2006


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