ACE-031

Mechanism (as reported)

A study described ACE-031 as binding myostatin and related negative regulators of muscle mass, as part of a strategy to disrupt inhibitory signaling to muscle development (PMIDs: 23169607, 27462804). Preclinical work reported skeletal muscle growth effects consistent with inhibition of negative regulators via soluble activin type IIB receptor (ACE-031) (PMID: 20466801).

Key findings (each cites a source)

• A study on black-market ACE-031 products reported that among 14 tested products, 12 contained an ACVR2B-immunoreactive protein, but further analyses indicated that the products contained full-length human activin receptor IIB rather than ACE-031, and that an Fc-fusion protein was not cleavable by IdeS protease. [PMID 40312924]
• The same black-market product study reported that a detection protocol developed for luspatercept in human serum could also detect black-market ACE-031. [PMID 40312924]
• In rat serum, the black-market ACE-031 was reported as detectable up to 48 h post administration in that study context. [PMID 40312924]
• A randomized, double-blind, placebo-controlled single ascending-dose study in 48 healthy postmenopausal women reported ACE-031 as generally well-tolerated, with injection site erythema among adverse events. [PMID 23169607]
• In that single-dose healthy-volunteer study, mean ACE-031 AUC and Cmax were reported to increase linearly with dose, and mean T1/2 was reported as 10–15 days. [PMID 23169607]
• That same study reported statistically significant increases in mean total body lean mass (3.3% by DXA) and thigh muscle volume (5.1% by MRI) at day 29 in a higher-dose group, and reported statistically significant changes in serum biomarkers suggesting improved bone and fat metabolism. [PMID 23169607]
• A randomized, placebo-controlled clinical trial in ambulatory boys with Duchenne muscular dystrophy reported that ACE-031 was not associated with serious or severe adverse events, but the study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias. [PMID 27462804]
• In that Duchenne muscular dystrophy trial, the authors reported trends for maintenance of 6-minute walk test distance and trends for increased lean body mass and bone mineral density and reduced fat mass, noting these were not statistically significant for the 6MWT outcome reported. [PMID 27462804]
• A preclinical mouse study reported that treatment with ACE-031 increased muscle mass measurements and reported that soleus fiber-type distribution was unchanged while fiber cross-sectional area increased in the reported muscles. [PMID 20466801]
• A review discussion of anti-myostatin approaches described ACE-031 as a myostatin decoy receptor concept among multiple strategies under investigation for myopathies, and noted that clinical application would need further evaluation of safety and disease targeting. [PMID 22277518]
• A sports drug testing review reported that myostatin receptor ligands including ACE-031 could be relevant for anti-doping controls and described the need for analytical strategies and analytical data to support identification in testing contexts. [PMID 26842585]