Myostatin and Activin A (MSTN, INHBA (gene), Activin A (protein))

Growth differentiation factor 8 (Myostatin) and Activin A are secreted protein ligands belonging to the transforming growth factor-β superfamily. Both are negative regulators of skeletal muscle growth, acting primarily by signaling through specific type I and type II activin receptors (ACVR2, ACVR2B, ALK4, and ALK5), which activate the intracellular Smad transcriptional pathway. Their activities are partially redundant, and simultaneous inhibition leads to greater increases in muscle mass than blockade of myostatin alone. These targets are of substantial therapeutic interest in treating muscle wasting, metabolic disorders, and certain degenerative or inflammatory conditions. Drug development efforts include ligand traps (ACE-031), monoclonal antibodies (bimagrumab, REGN2477), and follistatin-based inhibitors, all aiming to enhance muscle growth and improve metabolic health. Safety concerns center on specificity, as broad inhibition can disrupt roles of related family members and downstream signaling processes essential beyond muscle tissue.

Other names

Myostatin: GDF-8, MSTNActivin A: INHBA (gene), Activin A proteinBoth are also collectively referenced as TGF-β superfamily ligands in muscle biology contexts

Ligand trap: Sequesters myostatin/activin A, preventing receptor interaction; Monoclonal antibody: Blocks ligand binding or receptor activation; Decoy receptor: Binds to myostatin/activin A, inhibiting signaling; Follistatin proteins/binding proteins: Naturally inhibit both ligands