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

## TL;DR

ACE-031, a protein targeting muscle-regulating receptors, increased muscle mass and strength in marmosets, suggesting potential for treating muscle diseases in humans.

## Contribution

Demonstrates the efficacy of ACE-031 in increasing muscle mass and strength in a non-human primate model.

## Key findings

- ACE-031 significantly increased lean body mass in marmosets compared to controls.
- Biceps brachii showed increased cross-sectional area of both type I and type II muscle fibers.
- Ex vivo contractile properties of EDL muscles improved with ACE-031 treatment.

## Abstract

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.