Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of a protein called dystrophin that helps keep muscle cells intact. There is no cure, but physical therapy and corticosteroids reduce inflammation and help delay muscle decline, helping to relieve symptoms and improving quality of life. Newer gene-targeting treatments are being tested, but they remain limited to a small number of patients targeted. Now, Johns Hopkins Medicine researchers report that a drug first developed to treat kidney disease, blocks the ion channel called TRPC6 in genetically modified mice with severe or moderate Duchenne muscular dystrophy (DMD) prolongs survival and improves muscle function.

The new study, published in the Journal of Clinical Investigation-Insight in a paper titled, “Pharmacological TRPC6 inhibition improves survival and muscle function in mice with Duchenne muscular dystrophy.”

Their findings demonstrate that a drug blocking the ion channel called TRPC6 in mice with severe DMD doubled their survival and improved their skeletal and cardiac muscle function. The drug also reduced bone deformities associated with weak muscles.

“In 2014, my laboratory first showed that calcium entering heart muscle cells from Duchenne mice rose more when they were stretched as compared to normal cells. This induced abnormal rhythms. We found that blocking TRPC6 prevented this excess calcium from entering the heart and reduced arrhythmia,” said David Kass, MD, the Abraham and Virginia Weiss professor of cardiology at the Johns Hopkins University School of Medicine and senior author of the study. “We thought maybe a long-term TRPC6 blocker would help with this syndrome. Unfortunately, the drug we had back then worked fine in cells but was metabolized too fast in animals, so it was not usable.”

The researchers used a mouse model of DMD that mimics the severe disease found in humans. Heart function improved by nearly 50%, and the mice moved around 50% more and faster when compared with DMD mice that did not get the drug.

“We believe this may be one of the first studies to prolong survival in this very severe model of Duchenne with a compound that can be administered orally. While the molecule does not restore dystrophin, it blocks abnormal behavior of another protein that is caused by the lack of dystrophin,” explained Kass. “This is not a cure for Duchenne, but if human trials replicate these findings, it could mean patients may survive into their late 40s and 50s with the possibility for an improved quality of life.”

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