Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept-Study

PloS One
Patricia HafnerDirk Fischer

Abstract

Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7–10 years were treated with L-arginine (3 x 2.5 g/d) and metformin (2 x 250 mg/d) for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post-treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stres...Continue Reading

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Citations

Dec 5, 2017·The Tohoku Journal of Experimental Medicine·Sergej M Ostojic
Oct 6, 2018·British Journal of Clinical Pharmacology·Sam AminFinbar O'Callaghan
Dec 6, 2019·International Journal of Molecular Sciences·Libero VitielloMarcella Canton
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Feb 6, 2020·Life Science Alliance·Alessio ReggioFrancesca Sacco
Sep 16, 2019·Neuromuscular Disorders : NMD·Jessica F BoehlerCarl A Morris

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Methods Mentioned

BETA
biopsies
biopsy
X-Ray
ELISA
Protein Assay

Software Mentioned

SPSS
Odyssey

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