MDA RESEARCHERS USE GENE TRANSFER
TO REPAIR HEARTS OF MICE
WITH MUSCULAR DYSTROPHY

TUCSON, Ariz., Sept. 12, 2003 — Researchers supported by the Muscular Dystrophy Association have restored strength to fragile muscle cells in the hearts of mice with muscular dystrophy, using a gene transfer method that could eventually be tried in people with the disease.

MDA-funded investigators Dongsheng Duan at the University of Missouri in Columbia and Jeffrey Chamberlain at the University of Washington in Seattle delivered a highly miniaturized version of the gene for dystrophin, a protein that’s missing in Duchenne muscular dystrophy and deficient or abnormal in a related disorder, Becker dystrophy.

The findings are published in the Sept. 30 issue of the journal Circulation, released online to subscribers Sept. 2.

The MDA-supported researchers delivered the microdystrophin genes inside an adeno-associated virus (AAV), which has previously been used to safely deliver small genes to muscle tissue. Until now, the AAV was considered too small to carry the very large dystrophin gene, but it was able to accommodate the miniaturized microdystrophin molecule.

The investigators injected the virus-gene construct into the cardiac cavities of the dystrophin-deficient mice. From there, the injected genes entered heart muscle cells and allowed them to produce enough dystrophin to restore structural integrity to the muscle cell membrane for at least 10 months.

“The heart muscle is an important target for treatment in Duchenne and many other forms of muscular dystrophy,” said MDA Director of Research Development Sharon Hesterlee. “If we can strengthen the heart, we may be able to buy time to develop more systemic approaches that will treat muscle weakness throughout the body.”

Duchenne dystrophy, which affects some one in 3,500 boys, is a severe muscular dystrophy of childhood. It causes severe weakness and atrophy of muscles, including those that control breathing and the heart muscle. Death usually comes in the 20s and 30s from either respiratory or cardiac failure.

Becker dystrophy, the less severe MD variant, involves less overall weakness but can shorten life because of severe cardiac involvement.

Respiratory failure can be treated with assisted ventilation, but so far, nonsurgical treatments for the cardiac muscle deterioration have been only marginally successful, and most people with MD aren’t candidates for cardiac transplants.

Molecular biologist Duan said his group would likely conduct further mouse studies to improve the gene transfer, compare the microdystrophin effects to those of a full-length gene, and evaluate the effects of the transfer on the cardiovascular system as a whole.
“Then, if we get positive results, we may want to move on to the dystrophic dog and eventually to human patients,” Duan noted, estimating that human trials, if they occur, might be about five years away.

MDA is a voluntary health agency working to defeat more than 40 neuromuscular diseases through programs of worldwide research, comprehensive services, and far-reaching professional and public health education. The Association’s programs are funded almost entirely by individual private contributors.