ACE-031, a soluble activin type IIB receptor, increases muscle mass and strength in the common marmoset (Callithrix jacchus).

Pharmacological blockade of ligands for the activin receptor type IIB (ActRIIB) e.g., myostatin and activin A is associated with improvements in murine skeletal muscle mass and function. The efficacy of a similar treatment approach in a non-human primate (NHP) model would suggest a greater likelihood of success in the treatment of humans suffering from chronic myopathies. In the present study, we elucidate the potential therapeutic benefit of ACE-031, a therapeutic protein consisting of the ActRIIB extracellular region fused to human IgG1, in the common marmoset (Callithrix jacchus). Marmosets were randomized to receive ACE-031 or vehicle control (10 mM Tris buffered saline; TBS) for 14 weeks. Body composition was measured weekly throughout the experimental period and morphometric analysis and contractile properties of skeletal muscle were assessed terminally. There was a significant main effect of time and time x treatment interaction for lean body mass, such that marmosets administered ACE-031 were greater at euthanasia compared to baseline; this was not observed in the vehicle-treated controls. Biceps brachii exhibited a significant increase in the cross-sectional area of both type I and type II fibers and ex vivo contractile properties of the EDL showed an increase in absolute and specific force production. The efficacy of ACE-031 in non-human primates provides optimism that a therapeutic strategy that targets multiple negative regulators of skeletal muscle may be beneficial in treating myopathies in humans.