Antiviral Drug May Provide New Muscular Dystrophy Treatment
A research team led by Cincinnati Children’s scientists has found that an antiviral drug currently being tested to treat Hepatitis C may reduce muscle cell damage in Duchenne and other forms of muscular dystrophy (MD).
The investigational drug Debio-025 is currently undergoing human trials in Europe for treating Hepatitis C infections. The drug is a known inhibitor of the protein cyclophilin D, which triggers the mitrochondrial swelling leading to muscle fiber cell death in patients with MD.
Researchers decided to test the drug on MD after earlier laboratory tests showed that deleting a gene that encodes cycolphilin D reduced swelling and reversed or prevented the progressive muscle damage associated with the disease.
These findings led the research team to look for pharmacological treatments that also could inhibit cyclophilin D. The drug cyclosporine is a well-documented inhibitor of the protein, but its use is problematic because it also inhibits a protein, calcineurin, that is crucial to skeletal muscle cell development and.
The advantage of Debio-025 is that it inhibits cyclophilin D and blocks cell death in a number of situations, but does not suppress the immune system or block calcineurin.
“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,” explains Jeff Molkentin, Ph.D., corresponding author of the study and a researcher in the Division of Molecular Cardiovascular Biology at Cincinnati Children’s. “This is why we believe inhibiting cyclophilin D could be a new treatment strategy.”
Another advantage of the drug, says Dr. Molkentin, is its position within the drug testing pipeline. “Debio-025 has already passed Phase II clinical trials in Europe and is considered safe in people,” he says. “So we want to explore the possibility of conducting clinical trials in patients with Duchenne MD.”
