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Pharmacol Res. 2017 Nov;125(Pt B):122-131. doi: 10.1016/j.phrs.2017.09.001. Epub 2017 Sep 9.

Alisporivir rescues defective mitochondrial respiration in Duchenne muscular dystrophy.

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Department of Biomedical Sciences and CNR Neuroscience Institute, University of Padova, Padova, Italy.
Department of Biology, University of Padova, Padova, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Institute of Molecular Genetics, CNR, Bologna, Italy; SC Laboratory of Musculoskeletal Cell Biology, IOR-IRCCS, Bologna, Italy.
Department of Biomedical Sciences and CNR Neuroscience Institute, University of Padova, Padova, Italy. Electronic address:


Duchenne muscular dystrophy (DMD) is a severe muscle disease of known etiology without effective, or generally applicable therapy. Mitochondria are affected by the disease in animal models but whether mitochondrial dysfunction is part of the pathogenesis in patients remains unclear. We show that primary cultures obtained from muscle biopsies of DMD patients display a decrease of the respiratory reserve, a consequence of inappropriate opening of the permeability transition pore (PTP). Treatment with the cyclophilin inhibitor alisporivir - a cyclosporin A derivative that desensitizes the PTP but does not inhibit calcineurin - largely restored the maximal respiratory capacity without affecting basal oxygen consumption in cells from patients, thus reinstating a normal respiratory reserve. Treatment with alisporivir, but not with cyclosporin A, led to a substantial recovery of respiratory function matching improved muscle ultrastructure and survival of sapje zebrafish, a severe model of DMD where muscle defects are close to those of DMD patients. Alisporivir was generally well tolerated in HCV patients and could be used for the treatment of DMD.


Cyclophilin; Duchenne muscular dystrophy; Mitochondria; Permeability transition; Respiration

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