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Toxic molecule may cause most common type of muscular dystrophy

Doctors at the University of Virginia Health System have shown for the first time that getting rid of poisonous RNA (ribonucleic acid) in muscle cells can reverse myotonic dystrophy, the most common type of muscular dystrophy in adults.

About 40,000 people in the United States have myotonic muscular dystrophy (MMD). The disease can cause a slow, progressive wasting of the muscles, irregular heartbeat, cataracts and insulin resistance. Many people don't know they have MMD until their teens or twenties.

To prove the theory that toxic RNA is involved in myotonic muscular dystrophy, a research team led by Dr. Mani Mahadevan, a UVa pathologist, duplicated the disease in mice. "We showed in our mouse model that when you make this poisonous RNA the mice get various aspects of myotonic dystrophy," Mahadevan said. "Then, when you take away the toxic RNA, the mice get back to normal."

Mahadevan hopes the research might lead to new therapies for MMD in the next few years. "If we develop a therapy to silence the expression of the toxic RNA molecule, that would be a viable approach to treat people with myotonic muscular dystrophy," he said. Mahadevan's research in published in the September 2006 issue of Nature Genetics and can be found online at: http://www.nature.com/ng/index.html

Making RNA is the second step in the conversion of DNA into proteins that determine the function of the body's cells. Myotonic muscular dystrophy is the first example of a disease caused by toxic RNA.

In 1992, Mahadevan discovered the gene mutation that causes myotonic muscular dystrophy (type 1) as part of a research group in Canada. The mutation is an increased number of CTG repeats in a gene called DMPK. Everyone with myotonic muscular dystrophy has that mutation on chromosome 19, which is now part of a genetic, diagnostic test for myotonic dystrophy.

In their latest research, Mahadevan and c
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Source:University of Virginia Health System


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