title: Long-term blinded placebo-controlled study of SNT-MC17/idebenone in the dystrophin deficient mdx mouse: cardiac protection and improved exercise performance.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatric Neurology, University Hospitals Leuven, Herestraat, Leuven, Belgium.
authors.forename: Gunnar M
authors.initials: GM
authors.lastname: Buyse
authors.forename: Gerry
authors.initials: G
authors.lastname: Van der Mieren
authors.forename: Michael
authors.initials: M
authors.lastname: Erb
authors.forename: Jan
authors.initials: J
authors.lastname: D'hooge
authors.forename: Paul
authors.initials: P
authors.lastname: Herijgers
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jara
authors.forename: An
authors.initials: A
authors.lastname: Van Den Bergh
authors.forename: Luc
authors.initials: L
authors.lastname: Mertens
authors.forename: Isabelle
authors.initials: I
authors.lastname: Courdier-Fruh
authors.forename: Patrizia
authors.initials: P
authors.lastname: Barzaghi
authors.forename: Thomas
authors.initials: T
authors.lastname: Meier
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002316:Cardiotonic Agents; D003971:Diastole; D004280:Dobutamine; D004452:Echocardiography; D005355:Fibrosis; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000378:metabolism; D018482:Muscle, Skeletal / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D010919:Placebos; D016037:Single-Blind Method; D013997:Time Factors; D019210:Troponin I / Q000097:blood; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002316:Cardiotonic Agents; D010919:Placebos; D019210:Troponin I; D014451:Ubiquinone; D004280:Dobutamine; C036619:idebenone
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