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Cyclosporin A (CsA) is a powerful immunosuppressive drug, which has been proposed for DMD treatment. CsA also directly regulates the mitochondrial permeability transition pore (mPTP), which participates in cell death pathways through the inhibition of cyclophilin D. Here, we evaluated whether Debio 025, a cyclophilin inhibitor with no immunosuppressive activity, improves the dystrophic condition in a mouse model of DMD, through regulation of mPTP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach:<\/jats:title>\n                    <jats:p>\n                      The potency of Debio 025 to protect mouse dystrophic cells against mitochondria\u2010mediated death was assessed by caspase\u20103 activity and calcium retention capacity assays.\n                      <jats:italic>Mdx<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>5Cv<\/jats:italic>\n                      <\/jats:sup>\n                      mice (3\u2010week\u2010old) were treated daily by gavage for 2 weeks with Debio 025 (10, 30 or 100\u2003mg\u2003kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ), CsA (10\u2003mg\u2003kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) or placebo. The effects on muscle necrosis and function were measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results:<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      investigations showed protective effect of low concentrations of Debio 025 against cell death. Histology demonstrated that Debio 025 partially protected the diaphragm and soleus muscles against necrosis (10 and 100\u2003mg\u2003kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      , respectively). Hindlimb muscles from mice receiving Debio 025 at 10\u2003mg\u2003kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      relaxed faster, showed alteration in the stimulation frequency\u2010dependent recruitment of muscle fibres and displayed a higher resistance to mechanical stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications:<\/jats:title>\n                    <jats:p>Debio 025 partially improved the structure and the function of the dystrophic mouse muscle, suggesting that therapies targeting the mPTP may be helpful to DMD patients.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>British Journal of Pharmacology<\/jats:italic>\n                      (2008)\n                      <jats:bold>155<\/jats:bold>\n                      , 574\u2013584; doi:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.285\">10.1038\/bjp.2008.285<\/jats:ext-link>\n                      ; published online 21 July 2008\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/bjp.2008.285","type":"journal-article","created":{"date-parts":[[2008,7,21]],"date-time":"2008-07-21T06:06:17Z","timestamp":1216620377000},"page":"574-584","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["Investigation of Debio 025, a cyclophilin inhibitor, in the dystrophic\n                    <i>mdx<\/i>\n                    mouse, a model for Duchenne muscular dystrophy"],"prefix":"10.1111","volume":"155","author":[{"given":"J","family":"Reutenauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O 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