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Muscular dystrophy mouse model yields potential growth factor treatment

An altered mouse model of Duchenne muscular dystrophy, developed to have high levels of insulin-like growth factor I (IGF-I), has shown increases in muscle mass of at least 40 percent and other changes that could herald a possible treatment for secondary symptoms of the disease in humans. The new mouse, developed with support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the Muscular Dystrophy Association, has also resulted in reduced amounts of muscle-replacing fibrous tissue and enhanced biological pathways associated with muscle regeneration.

Duchenne muscular dystrophy, a genetic muscle-wasting disease caused by mutations in the gene for the protein dystrophin, results in repeated cycles of muscle damage and insufficient muscle regeneration, leading to gradual replacement of muscle by fibrous tissue. Since IGF-I is known to help regenerate muscle and enhance biological pathways for making proteins, the University of Pennsylvania's H. Lee Sweeney, M.D., and his colleagues tested its effects by creating a new mouse model a cross between a strain with muscular dystrophy symptoms and another with high levels of IGF-I. The hybrid mouse showed not only increases in muscle mass and muscle force generation, but also reduced muscle cell death, a combination that could have significant treatment implications.

"This is indeed good news for the muscular dystrophy community," said Stephen I. Katz, M.D., Ph.D., director of NIAMS. "The mouse model has helped our efforts against this disease more than once, and it looks like the search for answers has moved to another level."

The new mouse model offers an additional potential benefit, says Dr. Sweeney. "The combination of better muscle regeneration and less muscle wasting could lead to a better muscle capacity over time.

Less muscle effort would be needed to produce a required force, s
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Contact: Ray Fleming
flemingr@mail.nih.gov
301-496-8190
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
22-May-2002


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