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Mighty mice are less susceptible to muscular dystrophy gene's effects

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Duchenne muscular dystrophy is the most common muscular dystrophy and the most common inherited lethal disease of childhood, affecting 1 in 3,500 live male births. (The genetic mutation that causes it is found on the X chromosome, and so is "covered up" in girls, who have two X chromosomes.) There's no good treatment at this time, and few patients survive into adulthood.

Early in the disease in humans, the regenerative capacity of stem cells in muscle, known as satellite cells, keep up with the damage, but eventually the damaging factors win. The result is not just loss of muscle, but also its replacement with non-muscle tissues, essentially scar tissue and fat.

This scarring process, called fibrosis, is also seen in mice with the muscular dystrophy-causing mutation. The Hopkins team reports that loss of myostatin function significantly reduced the amount of fibrosis, suggesting that the muscle regenerative process was improved.

The Hopkins scientists hope to unravel the mechanism of muscle regeneration in mice with and without myostatin, possibly revealing even better targets for improving the process. They also plan to use special genetic manipulations to turn off the myostatin gene in adult mice, rather than at conception, to see if losing myostatin later in the course of muscular dystrophy is also beneficial.

Authors on the study are Wagner, Lee, Alexandra McPherron and Nicole Winik, all of The Johns Hopkins University School of Medicine. Funding was provided by the National Institutes of Health, the Duchenne Parent Project, and the Muscular Dystrophy Association.

Myostatin was licensed by The Johns Hopkins University to MetaMorphix, Inc., and sublicensed to Wyeth Pharmaceuticals, Inc. Lee and McPherron are entitled to a share of sales royalty received by the University from sales of this factor. Lee, McPherron and the University own MetaMorphix stock, which is subject to certain restrictions under
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
25-Nov-2002


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