Challenges and Future Prospects of Targeting Myostatin/Activin A Signaling to Treat Diseases of Muscle Loss and Metabolic Dysfunction

被引：13

作者：

Lee, Se-Jin ^{[1
,2
,7
]}

Bhasin, Shalender ^{[3
]}

Klickstein, Lloyd ^{[4
]}

Krishnan, Venkatesh ^{[5
]}

Rooks, Daniel ^{[6
]}

机构：

[1] Jackson Lab Genom Med, Farmington, CT USA

[2] Univ Connecticut, Sch Med, Dept Genet & Genome Sci, Farmington, CT USA

[3] Harvard Med Sch, Brigham & Womens Hosp, Boston Claude D Pepper Older Amer Independence Ctr, Res Program Mens Health Aging & Metab, Boston, MA USA

[4] Versanis Bio Inc, Oakland, CA USA

[5] Eli Lilly Inc, Indianapolis, IN USA

[6] Novartis Inst Biomed Res Inc, Translat Med, Cambridge, MA USA

[7] Jackson Lab Genom Med, 10 Discovery Dr, Farmington, CT 06032 USA

来源：

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 2023年 / 78卷

基金：

美国国家卫生研究院;

关键词：

Activin A; Metabolic dysfunction; Mobility-disability; Muscle loss; Myostatin; INCLUSION-BODY MYOSITIS; ANTIBODY LY2495655; DOUBLE-BLIND; BIMAGRUMAB; PLACEBO; SAFETY; EFFICACY; TRIAL; GDF11;

D O I：

10.1093/gerona/glad033

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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-& beta; 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.

引用

页码：S32 / S37

页数：6

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