Spotlight on Research for 2005

January 2005 (historical)

Scientists Come Step Closer to New Muscular Dystrophy Treatment

As many as 1 in 3,500 baby boys are born with Duchenne muscular dystrophy (DMD), a severe form of the disease that causes weakening and wasting of the muscles. Despite the best available treatment to minimize the effects of the disease - including advanced respiratory and cardiac care, physical therapy to keep joints mobile, braces for support and, in some cases, surgery to correct some problems associated with the disease - few people with DMD live past their early 30s.

Now, research supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) brings scientists a step closer to a treatment that targets the underlying mechanism of the disease: a deficiency of a muscle protein called dystrophin.

Tejvir S. Khurana, M.D., Ph.D., and his colleagues at the University of Pennsylvania have shown that injecting a fragment of a protein called heregulin improves the structure and function of muscles of mice that develop a disease similar to DMD. After injecting these mice with the heregulin fragment for three months, the mechanical properties of their muscles were improved, and they showed fewer sites of muscle degeneration and less muscle inflammation than those injected with an inert saline solution alone.

Previous research by Dr. Khurana and other researchers suggests that heregulin works by increasing the body's production of another muscle protein, utrophin, which is structurally and functionally similar to dystrophin. In laboratory animals, utrophin is produced in high levels before birth, but decreases to low levels by adulthood. By increasing utrophin production, scientists found they could halt muscle degeneration related to dystrophin deficiency in mice. Heregulin, they suspected, would serve as a substitute for deficient dystrophin. Apparently, their suspicion was correct.

Although there are many therapies in development for DMD, this has an advantage over others because it compensates for the loss of dystrophin by using the body’s own cells to produce and regulate utrophin as a natural substitute for dystrophin in maintaining muscle function.

While successful treatments for this deadly disease are years away, additions to the candidate therapeutic approaches - such as this one - improve the chances of discovering ways to incrementally improve the lives of those affected by this devastating disease.

The mission of 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 http://www.niams.nih.gov.

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Krag TO, et al. Heregulin ameliorates the dystrophic phenotype in mdx mice. Proceedings of the National Academy of Sciences 2004;101:13856-60