ACE-031 (Ramatercept)
discontinuedAlso known as: Ramatercept, ActRIIB-Fc
**Mechanism of Action** ACE-031 (Ramatercept) is a soluble fusion protein comprising the extracellular domain of activin receptor type IIB (ActRIIB) linked to the Fc region of human IgG. It functions as a decoy receptor, binding and neutralizing myostatin (GDF-8) and other TGF-β superfamily ligands such as activin A and GDF-11. By sequestering these ligands, ACE-031 prevents their interaction with endogenous ActRIIB receptors, thereby inhibiting downstream Smad2/3 signaling. This blockade reduces the negative regulation of muscle growth, promoting myoblast proliferation and differentiation, and increasing skeletal muscle mass. **Key Research Findings** Preclinical studies in murine models of Duchenne muscular dystrophy (DMD) demonstrated that ACE-031 treatment significantly increased muscle mass, fiber size, and grip strength. A Phase II clinical trial in boys with DMD (NCT01099761) showed dose-dependent increases in lean body mass and muscle function over 12 weeks. However, the trial was terminated early due to safety concerns, including reports of epistaxis, telangiectasias, and potential vascular adverse events. Subsequent analysis suggested off-target effects on non-muscle tissues, possibly due to broad ligand sequestration. No further clinical development has been pursued, and the compound remains discontinued. **Clinical Relevance** ACE-031 represented a promising approach to counteract muscle wasting in DMD by targeting the myostatin pathway. Its discontinuation highlights the challenges of systemic ActRIIB inhibition, including unintended vascular effects and the complexity of TGF-β superfamily signaling in non-muscle tissues. The findings underscore the need for more selective myostatin inhibitors or muscle-specific delivery strategies. Currently, no approved therapies utilize this mechanism, though related ActRIIB-Fc compounds (e.g., bimagrumab) continue to be investigated for other indications. For research purposes only — not medical advice.
Key data
Research & studies
ACE-031 significantly increased lean body mass over time compared to vehicle controls.; Biceps brachii showed increased cross-sectional area in both type I and type II muscle fibers.; EDL muscle exhibited increased absolute and specific force production ex vivo.; Targeting multiple negative regulators of skeletal muscle may benefit human myopathies.
ACE-031 increased body weight and lean body mass in marmosets compared to vehicle controls.; Biceps brachii showed increased cross-sectional area of both type I and type II muscle fibers.; Ex vivo EDL contractile properties demonstrated increased absolute and specific force production.; Efficacy in non-human primates supports potential for treating human chronic myopathies.
Of 14 black market products, 12 contained an ACVR2B-immunoreactive protein, but none were authentic ACE-031.; The 12 positive products contained full-length human activin receptor IIB instead of the Fc-fusion protein ACE-031.; The detection protocol for luspatercept was successfully applied to detect black market ACE-031.; In rats, black market ACE-031 was detectable in serum up to 48 hours post-administration at 10 mg/kg.
CSF secretion rate increased in hyperplasia and decreased in atrophy and severance groups.; CSF reabsorption rate increased in both atrophy and hyperplasia groups but not in the severance group.; No significant changes were observed in choroid plexus-CSF-related protein levels across groups.; Alteration of MDB-transmitted tensile force affects CSF secretion and reabsorption rates.
Hyperplasia of suboccipital musculature significantly increased intracranial pressure.; Surgically severing myodural bridge connections significantly decreased intracranial pressure.; Myodural bridges may play a functional role in cerebrospinal fluid dynamics.
ACE-031 was not associated with serious or severe adverse events.; Study stopped after second dosing regimen due to epistaxis and telangiectasias.; Trend for maintenance of 6-minute walk test distance in ACE-031 groups versus placebo decline.; Trends for increased lean body mass, bone mineral density, and reduced fat mass with ACE-031.
ACE-031 was generally well-tolerated with adverse events including injection site erythema.; Mean ACE-031 AUC and Cmax increased linearly with dose; mean half-life was 10-15 days.; At 3 mg/kg, total body lean mass increased by 3.3% (p=0.03) and thigh muscle volume by 5.1% (p=0.03) at day 29.; Statistically significant changes in serum biomarkers suggest improved bone and fat metabolism.
Frequently asked questions
What is ACE-031 (Ramatercept)?
**Mechanism of Action** ACE-031 (Ramatercept) is a soluble fusion protein comprising the extracellular domain of activin receptor type IIB (ActRIIB) linked to the Fc region of human IgG. It functions as a decoy receptor, binding and neutralizing myostatin (GDF-8) and other TGF-β superfamily ligands such as activin A an
How does ACE-031 (Ramatercept) work?
Soluble ActRIIB-Fc decoy receptor that sequesters myostatin and related ligands; trialed in muscular dystrophy before discontinuation.
What is the research status of ACE-031 (Ramatercept)?
ACE-031 (Ramatercept) is currently classified as discontinued, with 12 research references on record. This is for research purposes only and is not medical advice.
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Truncated IGF-1 variant with high local potency and short half-life, studied for site-specific muscle growth.
Activin-binding glycoprotein that antagonizes myostatin (GDF-8) to release the brake on skeletal muscle growth.
Long-acting IGF-1 analog with reduced IGFBP binding, prolonging activation of the IGF-1 receptor to drive muscle hypertrophy.
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