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Scientists discover 'needle in a haystack' for muscular dystrophy patients
Date:1/22/2013

membrane. What we found was that dystrophin has a special 'claw' that is used to grab nNOS and bring it to the muscle cell membrane. Now that we have that key, we hope to begin the process of developing a therapy for patients."

Duan and Lai, scientists with MU's Department of Molecular Microbiology and Immunology, found that two particular sections of the dystrophin gene must be present for nNOS to bind to the muscle cell membrane. The sections of the gene, known as "repeaters 16 & 17," contain a "claw" that can grab nNOS and bring it to the muscle cell membrane so that it will prevent ischemic damage from muscle activity. Without this "claw," nNOS doesn't bind to the cell membrane and the muscle cells are damaged, leading to further problems associated with muscular dystrophy.

The other key to this puzzle is dystrophin. If the protein is not present in the body, no "claw" exists and nNOS would never make it to the muscle cell membrane. For years, scientists have been attempting to find ways to make the body manufacture dystrophin, and thus get nNOS to the muscle cell membrane. Duan and Lai said the answer might lie elsewhere.

"Everybody, including those individuals with muscular dystrophy, has another protein known as 'utrophin,' " said Duan, a Margaret Proctor Mulligan Distinguished Professor in Medical Research at MU. "Utrophin is nearly identical to dystrophin except that it is missing repeaters 16 & 17, so it cannot attract nNOS to the muscle cell membrane. In our study, we were able to modify utrophin so that it had the repeaters, and thus, the ability to grab nNOS and bring it to the muscle cell membrane to protect muscle. Our study was completed in mice, but if we can do the same thing in larger animals, we could eventually have a therapy for humans with this devastating disease."

Harper described the MU research as "as an exquisite example of a basic study with
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Contact: Laura Gerding
gerdingla@health.missouri.edu
573-882-9193
University of Missouri School of Medicine
Source:Eurekalert  

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