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

ACE-031 treatment produced a significant main effect of time and time x treatment interaction for lean body mass in marmosets.

• Marmosets were randomized to receive ACE-031 or vehicle control (10 mM Tris buffered saline; TBS) for 14 weeks.
• Lean body mass was measured weekly throughout the experimental period.
• Marmosets administered ACE-031 showed greater lean body mass at euthanasia compared to baseline.
• This increase in lean body mass over time was not observed in vehicle-treated controls.

ACE-031 treatment significantly increased the cross-sectional area of both type I and type II muscle fibers in the biceps brachii.

• Morphometric analysis of skeletal muscle was assessed terminally.
• Both type I (slow-twitch) and type II (fast-twitch) fiber cross-sectional areas were significantly increased in the biceps brachii.
• This finding was based on histological analysis conducted at the end of the 14-week treatment period.

Ex vivo contractile properties of the extensor digitorum longus (EDL) showed increased absolute and specific force production following ACE-031 treatment.

• Contractile properties of the EDL were assessed ex vivo terminally after 14 weeks of treatment.
• Both absolute force production and specific force production (normalized measure) were increased in ACE-031-treated animals.
• This indicates functional improvement in muscle contractility beyond simply increased muscle mass.

ACE-031 is a therapeutic protein consisting of the ActRIIB extracellular region fused to human IgG1 that blocks ligands including myostatin and activin A.

• ACE-031 acts as a soluble decoy receptor for activin receptor type IIB (ActRIIB).
• Key ligands blocked by this mechanism include myostatin and activin A, which are negative regulators of skeletal muscle.
• Pharmacological blockade of ActRIIB ligands has been previously associated with improvements in murine skeletal muscle mass and function.
• The marmoset (Callithrix jacchus) model was selected as a non-human primate to assess likelihood of success in human therapeutic applications.

Body composition was measured weekly and morphometric and contractile assessments were conducted terminally in the marmoset study.

• The study duration was 14 weeks.
• Body composition was assessed weekly throughout the experimental period.
• Morphometric analysis and contractile properties of skeletal muscle were assessed at study termination (euthanasia).
• The common marmoset (Callithrix jacchus) was used as the non-human primate model.