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Nanoparticles treat muscular dystrophy in mice
Date:2/11/2014

Researchers at Washington University School of Medicine in St. Louis have demonstrated a new approach to treating muscular dystrophy. Mice with a form of this muscle-weakening disease showed improved strength and heart function when treated with nanoparticles loaded with rapamycin, an immunosuppressive drug recently found to improve recycling of cellular waste.

The study appears online in The FASEB Journal.

The investigators, including first author Kristin P. Bibee, MD, PhD, looked at a mouse model of Duchenne muscular dystrophy, the most severe inherited form of the disease. Duchenne exclusively affects boys who have to rely on wheelchairs by age 12 and die from heart or respiratory failure in their 20s.

The faulty gene that causes the disease prevents the body from producing dystrophin, a protein crucial for maintaining muscle cell integrity and function. The new study demonstrated that mice with muscular dystrophy, in addition to missing dystrophin, also can't recycle cellular waste, a process known as autophagy, or self-eating.

"Autophagy plays a major role in disposing of cellular debris," said senior author Samuel A. Wickline, MD, the James R. Hornsby Family Professor of Medicine. "If it doesn't happen, you might say the cell chokes on its own refuse. In muscular dystrophy, defective autophagy is not necessarily a primary source of muscle weakness, but it clearly becomes a problem over time. If you solve that, you can help the situation by maintaining more normal cellular function."

Though it's not clear how the missing dystrophin protein might be responsible for the muscle cells' poor housekeeping, the study showed that boosting autophagy improved skeletal muscle strength and heart function in these mice.

"Some investigators are looking for ways to replace dystrophin," said co-author Conrad C. Weihl, MD, PhD, associate professor of neurology. "But here we are focusing on the defect in autophagy
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Contact: Julia Evangelou Strait
straitj@wustl.edu
314-286-0141
Washington University School of Medicine
Source:Eurekalert  

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