Repurposing of drugs targeting mitochondrial oxidant production to treat Duchenne-related cardiomyopathy

Heart failure frequently develops in boys affected by Duchenne muscular dystrophy (DMD), but also in female carriers of dystrophin mutation. In cardiomyopathy associated with DMD, cardiac cells are progressively substituted by fibrous tissue and this inevitably leads to reduced contractile capacity. Unfortunately, current treatments for heart failure cannot cure DMD cardiomyopathy. Drug repurposing is a strategy for identifying new uses for approved drugs, especially useful for rare or orphan diseases because of the reduced costs and time leading to drug development. Among different drugs already used in the clinic, our group identified a few that could potentially prevent or attenuate Duchenne-associated cardiomyopathy. The goal of this project is to study the involvement of specific mitochondrial enzymes in the oxidative stress that affects DMD hearts and to test new therapies in male subjects, but also in female carriers of the disease. Specifically, the idea is that mitochondria, the powerhouse of the cell, can get damaged by free radicals resulting in cardiomyocyte death and cardiac dysfunction. By blocking oxidative stress, cardiac cells would likely be protected from cell death and cardiac function would be preserved. This study will assess the efficacy of specific, already marketed drugs on oxidative stress, mitochondrial as well as cardiac function in hearts affected by Duchenne-associated cardiomyopathy.