Myostatin (MSTN) (MSTN)

Myostatin, also known as Growth Differentiation Factor 8 (GDF8), is a member of the transforming growth factor-beta (TGF-beta) superfamily that serves as a critical negative regulator of skeletal muscle growth [11]. It is primarily produced in skeletal muscle cells and circulates in the blood in a latent form before being activated to bind to activin type II receptors, which triggers signaling pathways that inhibit muscle protein synthesis and promote protein degradation [2, 11]. Genetic mutations that lead to a lack of functional myostatin result in significantly increased muscle mass, a phenomenon observed in various species including cattle and humans [11]. Consequently, myostatin has become a major therapeutic target for treating muscle-wasting disorders such as facioscapulohumeral muscular dystrophy (FSHD) and spinal muscular atrophy (SMA), as well as metabolic conditions like obesity [1, 10, 12]. Drugs such as RO7204239 (emugrobart) are designed to bind and neutralize myostatin, particularly its latent form, to stimulate muscle hypertrophy and improve physical function [2, 7]. While RO7204239 showed successful target engagement in clinical trials, development for FSHD and SMA was recently discontinued due to a lack of meaningful clinical benefit, though investigations in obesity continue [7, 8, 15].

Other names

Growth differentiation factor 8GDF8GDF-8Pro-myostatinLatent myostatin

Inhibition of myostatin activity by binding to its latent or active form to prevent signaling through ActRIIB receptors, thereby promoting muscle hypertrophy and increasing muscle mass.