'Super-mouse' Gene Protects Against Duchenne Dystrophy in Mice

TUCSON, Ariz., March 31, 2002 – The Muscular Dystrophy Association-funded research team that used a muscle-building gene to create a breed of "super-mice" has shown that the same gene can largely protect mice from Duchenne muscular dystrophy (DMD).

DMD is the most common, and most deadly, childhood form of muscular dystrophy.

Last year, when the researchers gave normal mice a gene called muscle insulinlike growth factor 1 (mIgf1), the mice grew large muscles and resisted the muscle wasting that occurs with old age. Now, the scientists have introduced the gene into mice with DMD, and found that it counteracts the accelerated muscle wasting associated with the disease.

"The muscles stay in the state where kids [with DMD] are early in life," said lead researcher H. Lee Sweeney, a molecular biologist at the University of Pennsylvania in Philadelphia.

Sweeney said he envisions using a combination of gene therapy and stem cells to administer mIgf1 to youngsters with DMD. A virus could deliver the gene to stem cells grown in the lab, and those cells could be injected into the body, he explained.

"The really nice thing about this approach is that it doesn't depend on correcting the defective gene that causes Duchenne, so it has the potential for treating other forms of muscular dystrophy as well," said MDA Director of Research Development Sharon Hesterlee.

DMD is caused by mutations in the X chromosome gene encoding the muscle protein dystrophin, and almost exclusively affects boys. It causes progressive muscle wasting beginning in early childhood, and typically leads to death from respiratory failure in the 20s.

In mice, mIgf1 works by stimulating muscle stem cells to divide and build new muscle tissue. Diseased mice that were given the mIgf1 gene showed a 40 percent to 60 percent increase in the size and strength of their muscles compared to those mice not given mIgf1.

The mice given mIgf1 had larger, healthier-looking diaphragms (a chest muscle that controls breathing) with little evidence of scar tissue. This aspect of the finding is important, because deterioration of the diaphragm and other muscles involved in breathing is a leading cause of death in young men with DMD.

The study results were published in the April 1 issue of the Journal of Cell Biology.

Sweeney has entered discussions with biotechnology companies capable of producing the viruses and stem cells that will be needed to test mIgf1 in people.

MDA is the nonprofit health agency dedicated to curing muscular dystrophy, ALS and related diseases by funding worldwide research. The Association also provides comprehensive health care and support services, advocacy and education. The Association's programs are funded almost entirely by individual private contributors.