Pathology-associated activins and growth differentiation factors (Activins/GDFs)

The pathology-associated activins and growth differentiation factors (GDFs) are a subset of the transforming growth factor-beta (TGF-β) superfamily that play critical roles in regulating systemic homeostasis and are often upregulated in disease states. Key members include Activin A, Activin B, GDF-8 (myostatin), and GDF-11, which signal through type II activin receptors (ActRIIA and ActRIIB) to modulate processes such as erythropoiesis, muscle mass maintenance, and fibrotic responses (1, 2). In conditions like pulmonary arterial hypertension (PAH), myelodysplastic syndromes, and cancer cachexia, overproduction of these ligands leads to maladaptive signaling that drives disease progression (3, 4). Therapeutic strategies primarily involve "ligand traps," such as sotatercept and luspatercept, which consist of the extracellular domain of ActRIIA or ActRIIB fused to an IgG Fc fragment (5, 6). These agents sequester the circulating ligands, thereby restoring balance to the signaling pathways and treating the underlying pathology, such as improving red blood cell maturation or reducing pulmonary vascular resistance (2, 7).

Other names

Activin-related ligandsTGF-beta superfamily ligandsMyostatin and related GDFsInhibin beta subunitsActRII ligands

Sequestration of circulating ligands (ligand trap) to prevent activation of ActRIIA and ActRIIB receptors.