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UF scientists reverse muscle contractions in mouse model of muscular dystrophy

Gainesville, Fla. -- University of Florida scientists have used gene therapy to eliminate disabling muscle contractions in a mouse model of the most common form of adult-onset muscular dystrophy.

The inherited disorder, known as myotonic dystrophy, is found in one of every 8,000 people and causes skeletal muscles to lose the ability to relax once they contract.

"One of the principal manifestations of the disease is myotonia, or muscle hyperexcitability," said Maurice Swanson, Ph.D., the paper's senior author and a professor of molecular genetics and microbiology at UF's College of Medicine and the UF Genetics Institute. "So when patients with myotonic dystrophy contract one of the muscles in their arm, it's very difficult for them to release that contraction."

The muscles progressively weaken and eventually waste away. The disease also affects the heart muscle and is associated with irregular heart rhythms that can lead to sudden death. It also can result in cataracts, premature hair loss and mild to moderate mental retardation.

The work, to be published this week in the Proceedings of the National Academy of Sciences, builds on previous research at UF and the University of Rochester School of Medicine and Dentistry that revealed myotonic dystrophy is caused by malfunctioning genes that block the action of key proteins in cells, including one known as the muscleblind protein. These proteins, which help muscle and eye cells mature, stick to warped copies of RNA molecules that build up in a cell's nucleus and prevent the proteins from working properly.

In the current study, UF researchers used mice that carry the mutated genes and develop the muscle problems characteristic of myotonic dystrophy.

The scientists equipped the adeno-associated virus, or AAV-a safe and widely used vector in gene therapy-to express extra copies of the muscleblind protein. They then injected it into a muscle in the shin in the
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Contact: Melanie Fridl Ross
ufcardiac@aol.com
352-690-7051
University of Florida
17-Jul-2006


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