The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
J Gerontol A Biol Sci Med Sci. 2023 Jun 16;78(Suppl 1):32-37. doi: 10.1093/gerona/glad033.
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-β 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.
在过去的 25 年中，人们在阐明肌肉生长抑制素和其他属于转化生长因子-β超家族的分泌蛋白对骨骼肌质量的调控和信号机制方面取得了相当大的进展。临床前研究表明，靶向这些配体活性的潜在益处，推动了许多能够干扰这种信号通路并增加肌肉质量和功能的生物制剂的发展。这些生物制剂已经在许多临床试验中进行了测试，用于治疗多种以肌肉减少和脂肪过多为特征的适应症。在这里，我们回顾了这些试验的结果，并讨论了靶向这种信号通路治疗肌肉和代谢疾病的一些挑战和未来前景。肌肉生长抑制素抑制剂可以通过增加肌肉质量来改善代谢结果，而代谢紊乱可能是这些分子有吸引力的潜在适应症。
