ACE-031 (ACVR2B-Fc)

Overview

ACE-031 is a soluble form of the activin type IIB receptor (ActRIIB) fused to an IgG1 Fc domain. It functions as a decoy receptor, binding and neutralizing myostatin and other TGF-beta superfamily members that normally limit muscle growth. Originally developed by Acceleron Pharma for Duchenne muscular dystrophy (DMD),…

ACE-031 acts as a ligand trap for members of the TGF-beta superfamily. By mimicking the extracellular domain of the ActRIIB receptor, it intercepts myostatin (GDF-8), activin A, activin B, and GDF-11 before they can bind cell-surface receptors and activate Smad2/3 signaling. Blocking this pathway removes the natural…

Phase 1 data showed statistically significant lean mass increases (average +1.7%) after a single IV dose in healthy postmenopausal women.

Phase 2 trial in DMD patients showed improvements in lean body mass and bone mineral density, but trial was halted due to vascular adverse events.

Preclinical models demonstrate robust prevention of muscle loss in disease states through myostatin pathway inhibition.

Mechanism

No. ACE-031 is a soluble activin receptor that acts as a ligand trap, while follistatin directly binds myostatin. Both ultimately inhibit myostatin signaling, but through different mechanisms. Theoretically combined use might be synergistic, but clinical data on combinations doesn't exist.

Research areas

• ACE-031 is a soluble form of the activin type IIB receptor (ActRIIB) fused to an IgG1 Fc domain. It functions as a decoy receptor, binding and neutralizing myostatin and other TGF-beta superfamily members that normally limit muscle growth. Originally developed by Acceleron Pharma for Duchenne muscular dystrophy (DMD),…
• ACE-031 acts as a ligand trap for members of the TGF-beta superfamily. By mimicking the extracellular domain of the ActRIIB receptor, it intercepts myostatin (GDF-8), activin A, activin B, and GDF-11 before they can bind cell-surface receptors and activate Smad2/3 signaling. Blocking this pathway removes the natural…
• Phase 1 data showed statistically significant lean mass increases (average +1.7%) after a single IV dose in healthy postmenopausal women.
• Phase 2 trial in DMD patients showed improvements in lean body mass and bone mineral density, but trial was halted due to vascular adverse events.
• Preclinical models demonstrate robust prevention of muscle loss in disease states through myostatin pathway inhibition.

Research notes

• Nosebleeds (epistaxis) - most frequently reported adverse event
• Telangiectasia (dilated small blood vessels visible on skin)
• Minor injection site reactions
• Recurrent or severe nosebleeds
• Development of new or worsening telangiectasia

References

• pubmed.ncbi.nlm.nih.gov/28131562/
• pubmed.ncbi.nlm.nih.gov/15473835/
• pubmed.ncbi.nlm.nih.gov/23539721/
• pubmed.ncbi.nlm.nih.gov/24691811/

Questions