Key result
SNT-MC17/idebenone corrects diastolic dysfunction and prevents pump failure mortality vs placebo in mdx mice.
Why the study?
Duchenne muscular dystrophy is a severe incurable disease with heart failure as a leading cause of death, and long-term early-initiated therapeutic trials are challenging in humans.
Does idebenone improve cardiac function and prevent mortality in the mdx mouse model of Duchenne muscular dystrophy?
RCT
Blinded
Does idebenone improve cardiac function and prevent mortality in the mdx mouse model of Duchenne muscular dystrophy?
Long-term idebenone administration provides cardioprotection and improves exercise performance in a mouse model of Duchenne muscular dystrophy, suggesting a potential disease-modifying therapy.
Should not yet change practice in Duchenne cardiomyopathy; hypothesis-generating for idebenone in dystrophy models.
AIMS: Duchenne muscular dystrophy (DMD) is a severe and still incurable disease, with heart failure as a leading cause of death. The identification of a disease-modifying therapy may require early-initiated and long-term administration, but such type of therapeutic trial is not evident in humans. We have performed such a trial of SNT-MC17/idebenone in the mdx mouse model of DMD, based on the drug's potential to improve mitochondrial respiratory chain function and reduce oxidative stress. METHODS AND RESULTS: In this study, 200 mg/kg bodyweight of either SNT-MC17/idebenone or placebo was given from age 4 weeks until 10 months in mdx and wild-type mice. All evaluators were blinded to mouse type and treatment groups. Idebenone treatment significantly corrected cardiac diastolic dysfunction and prevented mortality from cardiac pump failure induced by dobutamine stress testing in vivo, significantly reduced cardiac inflammation and fibrosis, and significantly improved voluntary running performance in mdx mice. CONCLUSION: We have identified a novel potential therapeutic strategy for human DMD, as SNT-MC17/idebenone was cardioprotective and improved exercise performance in the dystrophin-deficient mdx mouse. Our data also illustrate that the mdx mouse provides unique opportunities for long-term controlled prehuman therapeutic studies.
No takes yet. Share an insight, caveat, or question.
Buyse et al. (2008) conducted an RCT in Duchenne muscular dystrophy (mdx mouse model). SNT-MC17/idebenone vs. placebo was evaluated on cardiac diastolic dysfunction, mortality from cardiac pump failure, cardiac inflammation and fibrosis, and voluntary running performance. SNT-MC17/idebenone significantly corrected cardiac diastolic dysfunction, prevented mortality from cardiac pump failure, and improved voluntary running performance in mdx mice compared to placebo.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: