ACE-031, a Soluble Activin Type IIB Receptor, Increases Muscle Mass and Strength in the Common Marmoset (Callithrix...

Area of Science:

• Muscle physiology
• Pharmacology
• Non-human primate models

Background:

• Activin receptor type IIB (ActRIIB) ligands like myostatin negatively regulate skeletal muscle.
• Blocking these ligands improves muscle in mice.
• Non-human primate (NHP) studies are crucial for human therapeutic translation.

Purpose of the Study:

• To evaluate the therapeutic potential of ACE-031 in the common marmoset (Callithrix jacchus).
• ACE-031 is a protein targeting ActRIIB ligands.
• To assess effects on skeletal muscle mass and function.

Main Methods:

• Marmosets received ACE-031 or vehicle control for 14 weeks.
• Weekly body composition analysis was performed.
• Terminal assessment included muscle morphometry and ex vivo contractile properties.

Main Results:

• ACE-031 treatment significantly increased body weight and lean body mass.
• Increased cross-sectional area of type I and type II muscle fibers in biceps brachii.
• Enhanced ex vivo contractile properties, including force production, in the EDL muscle.

Conclusions:

• ACE-031 demonstrated efficacy in a non-human primate model.
• Targeting multiple negative regulators of skeletal muscle holds therapeutic promise.
• This approach may benefit patients with chronic myopathies.