ubiquinone and Muscular-Dystrophy--Animal

Topics: Adolescent; Adult; Animals; Avitaminosis; Child; Child, Preschool; Creatine Kinase; Cricetinae; Deficiency Diseases; Electron Transport; Humans; Leukocytes; Male; Mice; Middle Aged; Mitochondria, Muscle; Muscles; Muscular Dystrophies; Muscular Dystrophy, Animal; Oxidoreductases; Rabbits; Succinate Dehydrogenase; Ubiquinone

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.. 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.. 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.

Topics: Animals; Antioxidants; Biomarkers; Cardiotonic Agents; Diastole; Dobutamine; Echocardiography; Fibrosis; Male; Mice; Mice, Inbred mdx; Mitochondrial Diseases; Muscle, Skeletal; Muscular Dystrophy, Animal; Myocardium; Oxidative Stress; Physical Conditioning, Animal; Placebos; Single-Blind Method; Time Factors; Troponin I; Ubiquinone

Topics: Adenosine Triphosphatases; Administration, Oral; Animals; Calcium; Calcium Radioisotopes; Chromatography, Thin Layer; Electric Stimulation; Electromyography; Energy Metabolism; Kidney; Liver; Mass Spectrometry; Mice; Mice, Inbred C3H; Mice, Inbred Strains; Muscles; Muscular Dystrophy, Animal; Myocardium; Sarcoplasmic Reticulum; Ubiquinone

Topics: Animals; Biological Transport; Deficiency Diseases; Electron Transport; Mitochondria, Muscle; Muscles; Muscular Dystrophy, Animal; Myocardium; Oxidative Phosphorylation; Oxidoreductases; Rabbits; Succinate Dehydrogenase; Ubiquinone; Vitamin E Deficiency

Topics: Animals; Creatine Kinase; Cricetinae; Depression, Chemical; Male; Muscles; Muscular Dystrophy, Animal; Peptide Hydrolases; Ubiquinone; Vitamin E Deficiency

Topics: Animals; Benzoates; Carbon Isotopes; Cholesterol; Lactones; Male; Mevalonic Acid; Mice; Mitochondria, Muscle; Muscles; Muscular Dystrophy, Animal; Squalene; Succinate Dehydrogenase; Ubiquinone

Topics: Animals; Hindlimb; Mice; Mitochondria, Muscle; Muscular Dystrophies; Muscular Dystrophy, Animal; Myocardium; Ubiquinone

Topics: Animals; Female; Hindlimb; Male; Mice; Muscles; Muscular Dystrophies; Muscular Dystrophy, Animal; Myocardium; Oxidoreductases; Succinate Dehydrogenase; Ubiquinone