ACE-031

A soluble form of the activin type IIB receptor fused to a human IgG1 Fc domain. It functions as a decoy receptor, binding myostatin, activin, GDF-11, and other TGF-beta superfamily ligands before they can signal through their natural receptors. Originally developed for Duchenne muscular dystrophy, trials were halted due to off-target vascular effects.

• Acts as a soluble decoy receptor for myostatin, activin A/B, GDF-11, and BMP-9/10
• Prevents ligand binding to membrane-bound ActRIIB, blocking Smad2/3 signaling
• Removes multiple parallel inhibitory pathways that limit muscle growth
• Off-target BMP-9/10 inhibition affects vascular endothelial signaling (responsible for side effects)

• Any bleeding disorder or anticoagulant therapy
• History of hereditary hemorrhagic telangiectasia (HHT)
• Cardiovascular disease or vascular abnormalities
• Pregnancy or breastfeeding
• Active malignancy

Store at 2–8°C (36–46°F) for up to 3 months. For long-term storage, keep at -20°C (-4°F). Once reconstituted, refrigerate and use within 7 days. Avoid freeze-thaw cycles.

A Phase II trial in boys with Duchenne muscular dystrophy (NCT01099761) showed dose-dependent increases in lean body mass and bone mineral density. However, the trial was discontinued due to epistaxis and telangiectasias attributed to off-target inhibition of BMP-9/10. Subsequent research by Acceleron led to more selective agents (luspatercept) that avoid the vascular side effects. ACE-031 remains a proof of concept for the ActRIIB pathway in muscle growth.