期刊
NATURE COMMUNICATIONS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-07058-4
关键词
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资金
- University of Geneva
- Swiss Foundation for Research on Muscle Diseases (SFRMD/FSRMM/SSEM)
- French Muscular Dystrophy Association (AFM-Telethon) [17821, 20959]
- Dutch Duchenne Parent Project (DPP-NL)
- INSERM, CNRS, Agence Nationale de la Recherche [ANR-14-CE12-0009, ANR-10-LABX-0030-INRT, ANR-10-IDEX-0002-02]
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant [800198]
- LabEx INRT funds
- University of Lausanne
- University of Strasbourg
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 Mtml-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.
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