Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy

Article Article scientifique Article Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy eng 2018 author Gayi Elinam 698884 author Neff Laurence Anne 638195 author Massana Muñoz Xènia author Ismail Hesham 693230 author Sierra Arregui Marta 899342 author Mercier Thomas author Décosterd Laurent A. author Laporte Jocelyn author Cowling Belinda S. author Dorchies Olivier 135677 author Scapozza Leonardo 600318 4848 10.1038/s41467-018-07058-4 30451843 2041-1723 http://www.nature.com/articles/s41467-018-07058-4 X-linked myotubular myopathy (XLMTM, also known as XLCNM) is a severe congenital muscular disorder due to mutations in the myotubularin gene, MTM1. It is characterized by generalized hypotonia, leading to neonatal death of most patients. No specific treatment exists. Here, we show that tamoxifen, a well-known drug used against breast cancer, rescues the phenotype of Mtm1-deficient mice. Tamoxifen increases lifespan several-fold while improving overall motor function and preventing disease progression including lower limb paralysis. Tamoxifen corrects functional, histological and molecular hallmarks of XLMTM, with improved force output, myonuclei positioning, myofibrillar structure, triad number, and excitation-contraction coupling. Tamoxifen normalizes the expression level of the XLMTM disease modifiers DNM2 and PI3KC2B, likely contributing to the phenotypic rescue. Our findings demonstrate that tamoxifen is a promising candidate for clinical evaluation in XLMTM patients. Tamoxifen X-linked myotubular myopathy XLMTM Dewey 615 31 Section des sciences pharmaceutiques 17 false Nature Communications 9 1 61901c99-ec3c-4cb9-bf48-1eba2d3aaf66 Article (Published version) Public Gayi_et_al_tamoxifen_myopathy_Nature_Commun_2018.pdf 4016731 application/pdf CC BY openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy	Nature Communications			2018	510	280

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