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Investigational drug tested for preventing muscle fiber death in muscular dystrophy
Date:3/16/2008

CINCINNATI An investigational antiviral drug currently undergoing human trials in Europe for treating Hepatitis C infections may have potential to reduce muscle cell damage in Duchenne and other forms of muscular dystrophy (MD). A research team led by Cincinnati Childrens Hospital Medical Center reported their results using three different mouse models of MD in a letter posted online March 16 by the journal Nature Medicine.

The investigational drug, Debio-025, is a known inhibitor of the protein cyclophilin D, which regulates the swelling of mitochondria in response to cellular injury. Researches decided to test the drug in mice engineered to carry MD after earlier laboratory tests showed deleting a gene that encodes cycolphilin D reduced swelling and reversed or prevented the diseases muscle-damaging characteristics. The mice were engineered as models of Duchenne muscular dystrophy and forms caused by a deficiency of two structural proteins, delta-sarcoglycan and laminin alpha2.

Similar to deleting the gene encoding cyclophilin D, we found that treatment with Debio-025 reduced mitochondrial swelling and necrotic manifestations in mice with muscular dystrophy. This is why we believe inhibiting cyclophilin D could be a new treatment strategy, said Jeff Molkentin, Ph.D., corresponding author of the study and a researcher in the Division of Molecular Cardiovascular Biology at Cincinnati Childrens. Debio-025 has already passed Phase II clinical trials in Europe and is considered safe in people, so we want to explore the possibility of conducting clinical trials in patients with Duchenne MD.

During the onset of muscular dystrophy, the loss of certain proteins critical to muscle function such as dystrophin can lead to contraction-related micro-tears in muscle fibers and an influx of calcium around muscle tissue. When this happens, cyclophilin D is instructed to make the membranes of mitochondria more permeable. This causes mitochondria t
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Contact: Nick Miller
513-803-6035
Cincinnati Children's Hospital Medical Center
Source:Eurekalert

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