Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-01486-4
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Funding
- National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust
- National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration (RD TRC)
- Association Francaise contre les Myopathies (AFM-Telethon), France [FSHS-42017-SG01]
- NIHR University College London Hospitals (UCLH) Biomedical Research Centre (BRC)
- University College London
- NIHR GOSH BRC
- Muscular Dystrophy UK
- Association Francaise contre les Myopathies (AFM-Telethon), France
- Myotubular Trust, UK
- FSH Society Grant [FSHS-42017-SG01]
- Medical Research Council [MR/K000608/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0515-10022] Funding Source: researchfish
- MRC [MR/K000608/1] Funding Source: UKRI
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Muscular dystrophies are characterized by weakness and wasting of skeletal muscle tissues. Several drugs targeting the myostatin pathway have been used in clinical trials to increase muscle mass and function but most showed limited efficacy. Here we show that the expression of components of the myostatin signaling pathway is downregulated in muscle wasting or atrophying diseases, with a decrease of myostatin and activin receptor, and an increase of the myostatin antagonist, follistatin. We also provide in vivo evidence in the congenital myotubular myopathy mouse model (knock-out for the myotubularin coding gene Mtm1) that a down-regulated myostatin pathway can be reactivated by correcting the underlying gene defect. Our data may explain the poor clinical efficacy of anti-myostatin approaches in several of the clinical studies and the apparent contradictory results in mice regarding the efficacy of anti-myostatin approaches and may inform patient selection and stratification for future trials.
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