DMD, BMD: Nationwide Children's Podcast Explores Dystrophin's Interactions

In a December 2012 podcast from Nationwide Children's Hospital, cell biologist Federica Montanaro discusses her team's recent progress in understanding how various proteins interact with dystrophin and how these interactions differ in the heart versus the skeletal muscles.

Dystrophin is the protein that's missing in Duchenne muscular dystrophy (DMD) and deficient in Becker muscular dystrophy (BMD).

The approximately 15-minute podcast is based on a paper by Montanaro and colleagues, published online Aug. 24, 2012, in PLOS One. (See Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins.) A transcript will be provided along with the podcast on the Nationwide site in the section called This Month in Muscular Dystrophy.

Montanaro is a principal investigator in the Center for Gene Therapy at Nationwide Children's Hospital in Columbus, Ohio, and is an assistant professor in the Department of Pediatrics at the Research Institute at Nationwide Children's and at Ohio State University.

She's interviewed by Kevin Flanigan, a specialist in neuromuscular disorders and a principal investigator in the Center for Gene Therapy at Nationwide. Flanigan also co-directs the MDA neuromuscular disease clinic at that institution.

Podcast summary

Montanaro describes how powerful new techniques used in molecular biology have allowed researchers to tease out exactly which proteins stick to ("bind") other proteins in a cell and how this technology has allowed greater understanding of dystrophin's usual role in the heart and skeletal muscles and what happens in dystrophin deficiency.

Montanaro says she hopes these new techniques will "fill in the gap in knowledge" of what happens between the loss of dystrophin and the death of a cell. Researchers, she says, know where the process "starts and where it ends" but that what happens in between has been "sort of a black box."

Better understanding of the "black box" could lead to trying existing or developing new drugs to compensate for dystrophin deficiency.

Specifically, Montanaro and colleagues have found that:

• In skeletal muscle fibers, dystrophin normally binds (indirectly) a protein called nNOS, which increases blood flow to exercising muscle; but in the heart, dystrophin does not appear to bind nNOS. The implication is that nNOS has a different role in the heart from the one it has in skeletal muscle fibers, a finding that could affect treatment.
• In the heart, dystrophin normally interacts with two ion channel proteins that it does not appear to interact with in skeletal muscles. Ion channels are pores through which charged particles flow, and abnormalities in the behavior of these channels can lead to cardiac rhythm disturbances. Understanding more about what happens to these channels when dystrophin is absent or deficient may shed light on the cardiac rhythm disturbances that can occur in DMD or BMD, with implications for treatment.
• In the heart, dystrophin normally interacts with two proteins that are involved with cardiac contractions; these proteins don't appear to interact with dystrophin in skeletal muscle fibers. Understanding more about these contractile proteins and what happens to them when dystrophin is deficient could improve treatment of the cardiac muscle deterioration (cardiomyopathy) often seen in DMD and BMD.