Spotlight on Research for 2004

August 2004 (historical)

Gene Therapy Reaches All Damaged Muscles in Muscular Dystrophy Mouse

Scientists supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), part of the Department of Health and Human Services' National Institutes of Health, have discovered and demonstrated in mice a method of delivering genetic therapy for muscular dystrophy (MD) and perhaps other diseases of the muscle or heart. Their research shows for the first time a method by which a corrected gene for dystrophin (a protein found in normal muscle tissue) can be delivered, using a safe and simple method, to all of the affected muscles of a mouse with a disease that resembles Duchenne muscular dystrophy.

In research reported in the August issue of Nature Medicine, the team of University of Washington, Seattle, scientists found that by giving a single injection of an adeno-associated viral (AAV) vector (a viral "vehicle" carrying a mini-dystrophin gene) into the bloodstream, they were able to deliver levels of dystrophin that produced dramatic improvement of dystrophy in muscles throughout the body. These included muscles of the heart and lungs as well as skeletal muscle, such as those of the arms and legs.

The scientists' previous work showed that muscular dystrophy could be prevented from occurring in a mouse model of the disease by replacing the gene for dystrophin, which is defective in people with the Duchenne form of the disease, with a corrected copy. They also showed that injecting a new dystrophin gene into a single diseased muscle could improve the health of that one muscle. However, until now, no one had found a method in which a new gene could be delivered to all muscles of an adult animal, including muscles that had already developed muscular dystrophy.

By injecting the vector carrying the gene along with vascular endothelium growth factor (a molecule that allows the vector to move through the blood vessel walls into the muscles), the researchers were able to get the genes to all of their intended sites.

"This finding gives a significant boost to our redoubled efforts to find answers for muscular dystrophy, a group of diseases for which there is no effective treatment" says NIAMS Director Stephen I. Katz, M.D., Ph.D.

The study's authors admit there are still some unknowns. For one, it is not known whether the dystrophy can be completely eliminated, says Jeffrey S. Chamberlain, Ph.D., the University of Washington neurology professor who led the team. "My guess is that the earlier we do this treatment, the better the results will be, but we are still testing that idea," he says. Also, the scientists question whether this technology will work in people. But answering that question is the research team's next goal. "Now that we have obtained proof that it is possible to deliver new genes body-wide to all the muscles of an adult animal, the immediate goal is to find out if we can extend this work to people."

Eventually, the benefits of the discovery could go well beyond an effective treatment for Duchenne muscular dystrophy. "While we have applied this method to deliver dystrophin, there is no reason why this same method could not be used to deliver a gene to treat any type of muscular dystrophy or, frankly, any diseases of muscles or the heart," says Chamberlain.

Muscular dystrophy refers to a group of genetic diseases characterized by progressive weakness and degeneration of the skeletal or voluntary muscles which control movement. The muscles of the heart and some other involuntary muscles are also affected in some forms of MD, and a few forms involve other organs, as well.

The Muscular Dystrophy Association also helped fund this research.

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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Gregorevic P, et al. Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat Med 2004;10:828-834.