Scientists supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have used gene therapy to restore muscle function in a hamster model of limb-girdle muscular dystrophy (LGMD), a group of degenerative muscular diseases caused by mutations in the gene for the protein δ-sarcoglycan. The work has implications for treating the human forms of this and other muscular dystrophies.
A group of investigators led by NIAMS grantee Xiao Xiao, Ph.D., at the University of Pittsburgh injected a virus vector (adeno-associated virus, or AAV) bearing corrected copies of the gene into a leg muscle of the hamster LGMD model. The result was over 97 percent recovery in muscle strength in the dystrophic animals compared with normal hamsters. Treated animals also regained normal muscle weight and size and showed improvement in muscle cell condition. Furthermore, the treatment conferred protection from muscle loss.
"This work, coupled with other recent advances, signals a brighter day for those with many forms of muscular dystrophy," said NIAMS Director Stephen I. Katz, M.D., Ph.D. "Animal model research like this points to gene therapy as a likely candidate for treating some human muscle diseases."
The study, according to the authors, "is the first report of successful functional rescue of an entire muscle after AAV-mediated gene delivery." But since muscle is one of the larger human organs, they add, successful transfer of this technology to patients will depend in part on producing and delivering large amounts of the vector safely.
The muscular dystrophies are a group of genetic diseases characterized by progressive weakness and degeneration of the skeletal or voluntary muscles that control movement. LGMD usually begins in the teenage or early adult years and commonly progresses from the hips through the shoulders, arms, and legs, affecting mobility.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases 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.
Xiao X, Li J, Tsao Y-P, Dressman D, Hoffman E, Watchko J. Full functional rescue of a complete muscle (TA) in dystrophic hamsters by adeno-associated virus vector-directed gene therapy. Journal of Virology 74:1436-1442, 2000.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH), leads the Federal medical research effort in arthritis and musculoskeletal and skin diseases. The NIAMS supports research and research training throughout the United States, as well as on the NIH campus in Bethesda, MD, and disseminates health and research information. The National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse (NAMSIC) is a public service sponsored by the NIAMS that provides health information and information sources. Additional information can be found on the NIAMS Web site at http://www.niams.nih.gov/.