ACE-031

Overview

ACE-031 is a soluble fusion protein of the ActRIIB extracellular domain and human IgG1 Fc. It functions as a decoy receptor sequestering myostatin, activin, and other TGF-beta ligands to promote muscle growth.

Mechanism of Action

ACE-031 traps myostatin, activin A/B, GDF-11, and BMP-9/10 before they can engage membrane-bound ActRIIB, blocking Smad2/3 signaling and muscle atrophy gene expression (MuRF1, MAFbx). The IgG1-Fc extends half-life to ~10-15 days. The broad binding profile produces potent anabolic effects but also BMP-9/10-related vascular considerations.

Research Summary

Phase II DMD trial showed significant lean mass and bone density increases at 3mg/kg biweekly, but was halted due to epistaxis and telangiectasia from BMP-9/10 inhibition (Campbell et al., Muscle & Nerve, 2017). Phase I in postmenopausal women showed dose-dependent lean mass increases up to 3.3% (Attie et al., JBMR, 2011). Clinical development discontinued.

Dosing Information

Reported Side Effects

• Epistaxis (nosebleeds)
• Telangiectasias (small dilated blood vessels near skin surface)
• Gingival bleeding
• Mild erythema at injection site
• Transient increase in follicle-stimulating hormone

Research References

• Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial (2017)
• A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers (2013)