MDA-Supported Researcher Saves Respiratory Muscles in Muscular Dystrophy

TUCSON, Ariz., June 27, 2001 -- In a significant step toward a lifesaving treatment for Duchenne muscular dystrophy, researchers funded by the Muscular Dystrophy Association announced that they've used gene therapy to protect vital respiratory muscles in mice with the disease.

Wasting of the diaphragm, the muscle that powers the lungs, is a major cause of death in DMD. The new research, conducted by MDA grantee Leaf Huang and his colleagues at the University of Pittsburgh, provides the first demonstration that the diaphragm can be rescued by intravenous injection of a gene for dystrophin, which is defective in people with DMD.

"Dr. Huang's research is exciting for us at MDA because it establishes that gene therapy has the potential to extend the lives of people with DMD," said Sharon Hesterlee, MDA director of research development.

Duchenne MD is the most common and most fatal childhood form of muscular dystrophy. Affecting boys almost exclusively, it usually proves fatal by the 20s as heart and respiratory muscles are destroyed.

In previous studies on DMD gene therapy, researchers have packaged a functioning dystrophin gene into viruses, and injected the gene-laden viruses directly into the limb muscles of mice. While that technique seems to preserve limb muscle function effectively, Huang feared that a diaphragm injured by DMD would be too fragile to withstand the injection procedure.

Huang injected "naked" DNA, without a virus, into the tail veins of the DMD mice. By surgically clamping a vein that siphons blood from the diaphragm, he created enough pressure to force the DNA into the muscle.

Although DNA in the blood is rapidly destroyed, the surgery only lasts a few seconds, so "all the action is over before the DNA is degraded," said Huang.

After the treatment, the diaphragm muscles of the mice showed stable expression of the dystrophin gene for as long as six months. The treated muscles were also able to resist degeneration: In untreated mice, 25 percent of cells in the diaphragm showed signs of degeneration, but in treated mice, that number dropped to 2 percent after just one week.

Huang said that, with some slight modifications to the surgical procedure, he believes his gene therapy technique could someday be used to treat people with DMD. But first, the technique will require further animal testing.

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.

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