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Improved muscle function in Duchenne muscular dystrophy through L-arginine and metformin: an investigator-initiated, open-label, single-center, proof-of-concept-study


Hafner, P and Bonati, U and Erne, B and Schmid, M and Rubino, D and Pohlman, U and Peters, T and Rutz, E and Frank, S and Neuhaus, C and Deuster, S and Gloor, M and Bieri, O and Fishcmann, A and Sinnerich, M and Gueven, N and Fischer, D, 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, 11, (1) Article e0147634. ISSN 1932-6203 (2016) [Refereed Article]


Copyright Statement

Copyright: 2016 Hafner et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1371/journal.pone.0147634


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 710 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 stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients.

Item Details

Item Type:Refereed Article
Keywords:Duchenne muscular dystrophy, therapy, mitochondria
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Clinical pharmacology and therapeutics
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the health sciences
UTAS Author:Gueven, N (Dr Nuri Guven)
ID Code:106105
Year Published:2016
Web of Science® Times Cited:41
Deposited By:Pharmacy
Deposited On:2016-01-29
Last Modified:2022-08-29
Downloads:206 View Download Statistics

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