ACE-031

ACE-031 works by soaking up myostatin and related proteins that normally put a brake on muscle growth, so blocking them can increase muscle mass. It's a lab-engineered "decoy" protein, not a small peptide, made from a piece of the activin receptor fused to part of an antibody. It was developed as a potential treatment for muscle-wasting diseases like Duchenne muscular dystrophy, but its clinical development was stopped after a trial found vascular side effects, and it's not FDA-approved. It's also banned in drug-tested sport.

ACE-031 was developed to build muscle by blocking myostatin and related signals that limit muscle growth. In a Phase 1 study in 48 healthy postmenopausal women, the highest dose was associated with small increases in lean body mass (~3.3%) and thigh muscle volume (~5.1%) and was generally well tolerated. A Phase 2 trial in boys with Duchenne muscular dystrophy showed trends toward preserved walking distance and lean mass but was stopped early over non-muscle safety signals — nosebleeds and small dilated blood vessels — and development was discontinued.

Not FDA-approved for any indication. Investigational; clinical development was discontinued by the sponsor (Acceleron Pharma). The Phase 1 studies completed; the Phase 2 Duchenne muscular dystrophy trials were terminated over vascular safety signals and the program was not restarted. WADA status: Prohibited at all times. The WADA Prohibited List names ACE-031 by name under S4.3, "Agents Preventing Activin Receptor IIB Activation" (as an example of a decoy activin receptor). Not DEA-scheduled.

ACE-031 is not FDA-approved and its development was stopped because of safety signals — notably nosebleeds and telangiectasias, thought to reflect effects on blood vessels because ActRIIB ligands act beyond muscle. It is prohibited in sport at all times: ACE-031 is named on the WADA Prohibited List under S4.3, "Agents Preventing Activin Receptor IIB Activation." There is no validated human dose for non-medical use. VialWise is a research and educational reference, not medical advice.

⚠️ For research and educational purposes only. ACE-031 is not approved by the FDA for any indication, and its clinical development was discontinued. Information here is informational, not medical advice. Always confirm any dose calculation with the in-app calculator and consult appropriate professional guidance.

⚠️ Development was stopped over safety signals. The Phase 2 Duchenne muscular dystrophy trial was halted early because of epistaxis (nosebleeds) and telangiectasias (dilated small blood vessels) — off-target effects attributed to the fact that ActRIIB ligands act well beyond muscle, including on blood vessels.[²] The sponsor discontinued the program. This is not a compound with an established safe human use.

⚠️ Prohibited in sport at all times (WADA S4.3). The WADA Prohibited List section S4.3, "Agents Preventing Activin Receptor IIB Activation," names ACE-031 explicitly as an example of a decoy activin receptor. It is prohibited both in and out of competition. Researchers in regulated sport should verify current status with their anti-doping organization.

ACE-031 (development name; also referred to as ramatercept) is not a classic short peptide but an engineered fusion protein: the extracellular, ligand-binding portion of the activin receptor type IIB (ActRIIB) fused to the Fc region of human IgG1. It was developed by Acceleron Pharma.[¹][²]

Mechanism — a myostatin/activin ligand trap. Muscle mass is held in check by myostatin and related TGF-β-superfamily proteins (activins, GDF-11), which signal through ActRIIB. ACE-031 is a soluble decoy receptor: by binding those ligands in circulation before they reach the real receptor, it releases the brake on muscle growth, increasing muscle mass. Unlike antibodies that hit myostatin alone, ACE-031 traps multiple ActRIIB ligands — which broadens its effect but also underlies its off-target vascular signals, since these ligands act beyond muscle.[¹][²]

Human evidence. According to PubMed, ACE-031 reached human trials: - A Phase 1 single-ascending-dose study in 48 healthy postmenopausal women ( subcutaneously, or placebo) reported it was generally well tolerated, with a mean half-life of 10–15 days. At the dose there were statistically significant increases in total-body lean mass (~3.3%, by DXA) and thigh muscle volume (~5.1%, by MRI) at day 29, plus biomarker changes suggesting effects on bone and fat metabolism.[¹] - A Phase 2, randomized, double-blind, placebo-controlled, ascending-dose trial in ambulatory boys with Duchenne muscular dystrophy administered ACE-031 subcutaneously every 2–4 weeks. It showed trends toward maintained 6-minute walk distance, increased lean mass and bone density, and reduced fat mass — but none reached statistical significance, and the study was stopped after the second dosing regimen because of potential safety concerns: epistaxis (nosebleeds) and telangiectasias.[²]

Evidence quality. ACE-031 has early human data (Phase 1 and an incomplete Phase 2) but the muscle-benefit signals were modest or non-significant, and the program was discontinued for safety. It is therefore best understood as a compound whose development was halted, not one with an established therapeutic profile.

Regulatory status (US). ACE-031 is not FDA-approved and is not DEA-scheduled. Clinical development was discontinued; it is available only as a research-supply material outside the FDA-recognized supply chain. On ClinicalTrials.gov the sponsor is now listed as Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., and no ACE-031 trial is active — both Duchenne muscular dystrophy studies are recorded as TERMINATED (NCT01099761; open-label extension NCT01239758), while the two Phase 1 studies (NCT00755638; NCT00952887) are recorded as COMPLETED.

Regulatory status (sport — WADA). ACE-031 is prohibited at all times. The WADA Prohibited List names ACE-031 by name under S4.3, "Agents Preventing Activin Receptor IIB Activation," as an example of a decoy activin receptor. Verify current status via the WADA Prohibited List and your National Anti-Doping Organization.

Common research interests. Myostatin inhibition for muscle mass in muscle-wasting conditions (the original clinical rationale), and — in the research community — muscle growth and body-composition change. These are extrapolated from halted early trials; there is no approved indication.

Commonly reported

• Epistaxis (nosebleeds) and telangiectasias (dilated small blood vessels) — the safety signals that stopped the DMD Phase 2; attributed to ActRIIB ligand trapping affecting blood vessels[²]
• Injection-site erythema (reported in Phase 1)[¹]
• Broad ligand trapping. Because ACE-031 traps multiple ActRIIB ligands (not myostatin alone), effects on bone, fat, vasculature, and other tissues are expected — the vascular signals are the clearest example.
• Immunogenicity. As a foreign Fc-fusion protein, anti-drug antibodies are a general concern for this class.
• Unknown long-term safety. No completed long-term human dataset exists.

Vascular / bleeding concerns — the epistaxis and telangiectasia signals make ACE-031 a specific concern for anyone with bleeding tendencies or vascular disease

Pregnancy and lactation — no data; default to contraindicated

Pediatric use — the only pediatric exposure (DMD boys) was halted for safety; should not be used in researchers under 18 outside a trial

Known hypersensitivity — contraindicated

Regulatory note (US): Not FDA-approved; development discontinued; available only as research-supply material outside the FDA-recognized supply chain. Not DEA-scheduled.

Regulatory note (sport): Prohibited at all times under WADA S4.3 (Agents Preventing Activin Receptor IIB Activation), where ACE-031 is named explicitly. Verify with your anti-doping organization before use.

Myostatin

A natural protein that acts as a brake on muscle growth. Blocking it tends to increase muscle mass — the target of ACE-031.

Activin receptor type IIB (ActRIIB)

The receptor that myostatin and related proteins bind to. ACE-031 is a soluble decoy version of this receptor that traps those proteins before they can signal.

Ligand trap / decoy receptor

An engineered molecule that binds up a signaling protein so it can't reach its real receptor — here, mopping up myostatin and activins.

Telangiectasia

Small, dilated blood vessels visible near the skin surface. These, along with nosebleeds, were part of the safety signal that stopped the DMD trial.

Fusion protein

A single molecule engineered by joining two protein pieces — here, part of a receptor joined to part of an antibody (Fc) to extend its lifetime in the body.

1. Attie KM, Borgstein NG, Yang Y, Condon CH, Wilson DM, Pearsall AE, Kumar R, Willins DA, Seehra JS, Sherman ML. (2013). A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle & Nerve, 47(3):416–423.(PMID 23169607 · NCT00755638)
2. Campbell C, McMillan HJ, Mah JK, Tarnopolsky M, Selby K, McClure T, Wilson DM, Sherman ML, Escolar D, Attie KM. (2017). Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial. Muscle & Nerve, 55(4):458–464.(PMID 27462804 · NCT01099761)

• AICAR — same mechanism class
• 5-amino-1MQ — same mechanism class
• SLU-PP-332 — same mechanism class
• Follistatin — shared research area
• HGH (Human Growth Hormone) / Somatropin — shared research area
• IGF-1 LR3 — shared research area