Challenges and Future Prospects of Targeting Myostatin/Activin A Signaling to Treat Diseases of Muscle Loss and Metabolic Dysfunction.
Se-Jin LeeShalender BhasinLloyd KlicksteinVenkatesh KrishnanDaniel RooksPublished in: The journals of gerontology. Series A, Biological sciences and medical sciences (2023)
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-ß 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.
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