MDA SCIENTISTS PROVE GENE THERAPY CAN PREVENT AGE-RELATED MUSCLE LOSS
(Opportunities Arise For Disease Treatment, Athletic And Cosmetic Enhancements)
TUCSON, Ariz., Dec. 14, 1998 -- Muscular Dystrophy Association-funded researchers have identified a gene therapy strategy to permanently prevent age-related loss of muscle mass and strength. Their data suggest the technique might counter the muscle-wasting effects of neuromuscular diseases, as age-related changes of the skeletal muscle are thought to mirror, at a slower rate, those that are seen in degenerative muscle disorders including muscular dystrophy. The gene therapy approach may also foster beneficial effects in humans for athletic or even cosmetic enhancements.
The team led by MDA grantee H. Lee Sweeney, professor of physiology at the University of Pennsylvania School of Medicine in Philadelphia, inserted the gene for insulin-like growth factor 1 (IGF-1) into mice. Their results -- presented today at the 38th annual meeting of the American Society for Cell Biology in San Francisco, and scheduled to be published in the Dec. 22 issue of the Proceedings of the National Academy of Sciences -- show the new treatment increased muscle strength by 15 percent in young adult mice and by 27 percent in older mice. The muscle size and strength in the treated older mice were indistinguishable from those of young untreated adult mice.
"These dramatic findings signal a 'fountain of youth' opportunity," said Leon Charash, chairman of MDA's Medical Advisory Committee. "Since mice, like humans, lose up to a third of their muscle mass and power with age, this technique should be explored for its rich potential to stave off advancing weakness, unsteadiness and impaired mobility among the elderly."
Charash also underscored that the finding opens up a whole new front in the war on degenerative muscle diseases.
MDA investigators have been making rapid progress toward clinical trials of gene therapy for muscular dystrophy using modified viruses to carry missing genes into muscle cells. "Since IGF-1 is a normally occurring gene," Charash added, "we've immediately begun the steps to see if it can provide therapeutic benefit by circumventing the immune response hurdle that must be cleared to deliver the genes, that when missing, cause muscular dystrophy and other neuromuscular diseases."
Previous studies have indicated that IGF-1 may play a role in the body's muscle repair mechanism by stimulating cell division. Yet they haven't shown injections of IGF-1 protein to be effective in preventing loss of muscle strength.
"Our ability to retain both muscle mass and muscle strength four months after injections probably hinges on the use of gene therapy to insert the IGF-I gene directly into the muscle," Sweeney said. "By harnessing the integration power of a modified adeno-associated virus, the procedure ensures that the IGF-1 protein is manufactured within the muscle compartment where it's needed."
IGF-1 is a growth factor critical in the process of muscle repair. Under normal circumstances, damaged muscles release quantities of IGF-1. The protein stimulates the transformation of neighboring muscle stem cells into functional muscle cells that migrate into the muscle to repair damage.
MDA is currently supporting Sweeney's study of the effects of IGF-1 gene therapy in a mouse model of muscular dystrophy.
The beneficial effects of this gene therapy could easily be used in humans for athletic or even cosmetic enhancements, Sweeney added. "I think the diseases where you might really see an effect are some of the milder muscular dystrophies, like Becker," Sweeney said.
He pointed out that some diseases of the nervous system that have muscle wasting as secondary effects, such as amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), may also benefit from treatment with the IGF-1 gene.
MDA grantee Antonio Musaro and colleagues at the Cardiovascular Research Center of Massachusetts General Hospital in Boston, collaborated with the University of Pennsylvania team led by Sweeney.
The nation's leading nongovernmental funder of research into neuromuscular diseases, MDA has staunchly supported the development of gene therapy as a potential treatment for muscular dystrophies and related disorders. The pioneering work by other MDA investigators (Penn, Ohio State University, University of Michigan, etc.) is expected to result in human clinical trials of gene therapy for muscular dystrophy early next year.
The first nonprofit organization honored with the American Medical Association Lifetime Achievement Award "for significant and lasting contributions to the health and welfare of humanity," MDA annually funds some 400 scientific teams worldwide and offers an unparalleled program of medical services through 230 MDA clinics nationwide.
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