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Long-term blinded placebo-controlled study of SNT-MC17/idebenone in the dystrophin deficient mdx mouse: cardiac protection and improved exercise performance

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...

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Detalles Bibliográficos
Autores principales: Buyse, Gunnar M., Van der Mieren, Gerry, Erb, Michael, D'hooge, Jan, Herijgers, Paul, Verbeken, Erik, Jara, Alejandro, Van Den Bergh, An, Mertens, Luc, Courdier-Fruh, Isabelle, Barzaghi, Patrizia, Meier, Thomas
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2639086/
https://www.ncbi.nlm.nih.gov/pubmed/18784063
http://dx.doi.org/10.1093/eurheartj/ehn406
Descripción
Sumario: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.