{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:05:51Z","timestamp":1792526751265,"version":"4.5.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG052962"],"award-info":[{"award-number":["R01AG052962"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR081659"],"award-info":[{"award-number":["R01AR081659"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 DK49296"],"award-info":[{"award-number":["RO1 DK49296"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R56AG052972"],"award-info":[{"award-number":["R56AG052972"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1AG072087"],"award-info":[{"award-number":["RO1AG072087"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Over the past 25 years, considerable progress has been made in terms of elucidating the regulatory and signaling mechanisms underlying the control of skeletal muscle mass by myostatin and other secreted proteins belonging to the transforming growth factor-\u03b2 superfamily. Preclinical studies demonstrating the potential benefits of targeting the activities of these ligands have fueled the development of numerous biologics capable of perturbing this signaling pathway and increasing muscle mass and function. These biologics have been tested in numerous clinical trials for a wide range of indications characterized by muscle loss and excess adiposity. Here, we review the results of these trials and discuss some of the challenges and future prospects for targeting this signaling pathway to treat muscle and metabolic diseases. Myostatin inhibitors may improve metabolic outcomes by increasing muscle mass, and metabolic disorders may be attractive potential indications for these molecules.<\/jats:p>","DOI":"10.1093\/gerona\/glad033","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T12:42:54Z","timestamp":1674650574000},"page":"32-37","source":"Crossref","is-referenced-by-count":45,"title":["Challenges and Future Prospects of Targeting Myostatin\/Activin A Signaling to Treat Diseases of Muscle Loss and Metabolic Dysfunction"],"prefix":"10.1093","volume":"78","author":[{"given":"Se-Jin","family":"Lee","sequence":"first","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine , Farmington, Connecticut , USA"},{"name":"Department of Genetics and Genome Sciences, University of Connecticut School of Medicine , Farmington, Connecticut , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3982-6200","authenticated-orcid":false,"given":"Shalender","family":"Bhasin","sequence":"additional","affiliation":[{"name":"Research Program in Men\u2019s Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloyd","family":"Klickstein","sequence":"additional","affiliation":[{"name":"Versanis Bio, Inc. , Oakland, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatesh","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Eli Lilly, Inc. , Indianapolis, Indiana , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rooks","sequence":"additional","affiliation":[{"name":"Translational Medicine, Novartis Institute for BioMedical Research, Inc. , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,16]]},"reference":[{"issue":"9","key":"2023061607531200900_CIT0001","doi-asserted-by":"crossref","first-page":"e148372","DOI":"10.1172\/JCI148372","article-title":"Targeting the myostatin signaling pathway to treat muscle loss and metabolic dysfunction","volume":"131","author":"Lee","year":"2021","journal-title":"J Clin Invest."},{"issue":"4","key":"2023061607531200900_CIT0002","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1016\/j.ajpath.2013.12.029","article-title":"Inhibition of activin A ameliorates skeletal muscle injury and rescues contractile properties by inducing efficient remodeling in female mice","volume":"184","author":"Yaden","year":"2014","journal-title":"Am J Pathol."},{"issue":"12","key":"2023061607531200900_CIT0003","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/S2213-8587(15)00298-3","article-title":"STEADY Group. Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial","volume":"3","author":"Becker","year":"2015","journal-title":"Lancet Diabetes Endocrinol."},{"issue":"1","key":"2023061607531200900_CIT0004","first-page":"62","article-title":"A phase 2 randomized study investigating the efficacy and safety of myostatin antibody LY2495655 versus placebo in patients undergoing elective total hip arthroplasty","volume":"5","author":"Woodhouse","year":"2016","journal-title":"J Frailty Aging"},{"issue":"9","key":"2023061607531200900_CIT0005","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1111\/jgs.14927","article-title":"Treatment of sarcopenia with bimagrumab: results from a phase II, randomized, controlled, proof-of-concept study","volume":"65","author":"Rooks","year":"2017","journal-title":"J Am Geriatr Soc."},{"issue":"10","key":"2023061607531200900_CIT0006","doi-asserted-by":"crossref","first-page":"e2020836e2020836","DOI":"10.1001\/jamanetworkopen.2020.20836","article-title":"Bimagrumab vs optimized standard of care for treatment of sarcopenia in community-dwelling older adults: a randomized clinical trial","volume":"3","author":"Rooks","year":"2020","journal-title":"JAMA Netw Open"},{"issue":"5","key":"2023061607531200900_CIT0007","doi-asserted-by":"crossref","first-page":"e263","DOI":"10.1016\/S2666-7568(21)00084-2","article-title":"Bimagrumab to improve recovery after hip fracture in older adults: a multicentre, double-blind, randomised, parallelgroup, placebo-controlled, phase 2a\/b trial","volume":"2","author":"Hofbauer","year":"2021","journal-title":"Lancet Hlthy Longevity"},{"issue":"5","key":"2023061607531200900_CIT0008","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/ana.21338","article-title":"A phase I\/IItrial of MYO-029 in adult subjects with muscular dystrophy","volume":"63","author":"Wagner","year":"2008","journal-title":"Ann Neurol."},{"issue":"6","key":"2023061607531200900_CIT0009","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.nmd.2020.05.002","article-title":"Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy","volume":"30","author":"Wagner","year":"2020","journal-title":"Neuromuscul Disord."},{"issue":"4","key":"2023061607531200900_CIT0010","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/mus.25268","article-title":"Myostatin inhibitor &#x2028;ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial","volume":"55","author":"Campbell","year":"2017","journal-title":"Muscle Nerve."},{"issue":"24","key":"2023061607531200900_CIT0011","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1212\/WNL.0000000000001070","article-title":"Treatment of sporadic inclusion body myositis with bimagrumab","volume":"83","author":"Amato","year":"2014","journal-title":"Neurology."},{"issue":"9","key":"2023061607531200900_CIT0012","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/S1474-4422(19)30200-5","article-title":"Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial","volume":"18","author":"Hanna","year":"2019","journal-title":"Lancet Neurol."},{"issue":"14","key":"2023061607531200900_CIT0013","doi-asserted-by":"crossref","first-page":"e1971","DOI":"10.1212\/WNL.0000000000010417","article-title":"Long-term safety and tolerability of bimagrumab (BYM338) in sporadic inclusion body myositis","volume":"95","author":"Sivakumar","year":"2020","journal-title":"Neurology."},{"issue":"5","key":"2023061607531200900_CIT0014","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/jcsm.12331","article-title":"LY2495655, an antimyostatin antibody, in pancreatic cancer: a randomized, phase 2 trial","volume":"9","author":"Golan","year":"2018","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"3","key":"2023061607531200900_CIT0015","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1164\/rccm.201802-0286OC","article-title":"Activin type II receptor blockade for treatment of muscle depletion in chronic obstructive pulmonary disease. 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