What it is
ACE-031 is an engineered protein built to block myostatin, the body's brake on muscle growth. It joins the outer, ligand-catching part of activin receptor type IIB (ActRIIB) to the Fc tail of a human antibody, which keeps it circulating for days. Acceleron Pharma developed it, later in partnership with Shire, as a treatment for Duchenne muscular dystrophy. Its non-proprietary name is ramatercept.
It is not a peptide. It is a large fusion protein, closer to a biologic drug than to anything else sold in a peptide vial.
How it works
Myostatin and several related proteins slow muscle growth by binding ActRIIB on muscle cells. ACE-031 is a free-floating copy of that receptor's binding end, so it acts as a decoy: the ligands bind the drug instead of the real receptor, and the brake on muscle is released.
The catch is that ActRIIB does not only bind myostatin. The Duchenne trial paper describes ACE-031 as binding myostatin and related ligands, and the side effects that ended the program were not in muscle at all.
What the research found
Healthy volunteers (Attie 2013)
In a double-blind, placebo-controlled study, 48 healthy postmenopausal women received a single subcutaneous dose of ACE-031 (0.02 to 3 mg/kg) or placebo. The drug's half-life was 10 to 15 days. At day 29, the 3 mg/kg group showed statistically significant increases in total lean body mass of 3.3% on DXA and in thigh muscle volume of 5.1% on MRI. Blood markers also suggested effects on bone and fat metabolism. The drug was generally well tolerated, with injection-site redness among the adverse events.
Duchenne muscular dystrophy (Campbell 2017)
The phase 2 trial enrolled ambulatory boys with Duchenne in Canada, randomised against placebo in ascending-dose cohorts. A 2011 conference abstract describes the first cohort at 0.5 mg/kg every four weeks and the second at 1 mg/kg every two weeks. Safety was the primary objective.
The study was stopped after the second dosing regimen because of nosebleeds, gum bleeding and telangiectasias, small dilated blood vessels in the skin. According to the Muscular Dystrophy Association, dosing had been on hold since February 2011 and the trial was terminated on 21 April 2011, with the extension study suspended. In May 2013 the companies announced that additional toxicology work did not support further development.
The published results showed that ACE-031 was not linked to serious or severe adverse events, and there were trends favouring the drug on six-minute walk distance, lean mass and bone mineral density. Because the trial stopped early, those trends were never confirmed.
Side effects reported in studies
- Healthy women: generally well tolerated after a single dose; injection-site redness was among the reported events.
- Duchenne boys: nosebleeds, gum bleeding and telangiectasias. None were classed as serious, but they were unexpected, not muscle-related, and in children with a chronic disease they were enough to halt the program.
These are the only human safety data. Nobody has studied repeated dosing in healthy adults.
ACE-031 vs follistatin-344
| ACE-031 | Follistatin-344 | |
|---|---|---|
| Mechanism | Decoy receptor that catches myostatin and related ligands | Natural binding protein for myostatin and activin |
| Best human data | Single-dose RCT in 48 women; phase 2 in Duchenne, stopped | Gene therapy in 6 Becker patients |
| Main safety signal | Bleeding and dilated skin vessels | None reported in the small gene therapy trial |
| Status | Development discontinued | Investigational |
Neither is a shortcut to muscle with a known safety profile. For what has been studied for muscle, ranked by evidence, see peptides for muscle growth and fat loss.
Status in the Philippines
ACE-031 was never approved in any country and is not registered with FDA Philippines. Clinical development ended in 2013, so anything sold online under the name comes from research-chemical suppliers, and anti-doping scientists have published methods for detecting black-market ACE-031. The WADA Prohibited List names decoy activin receptors such as ACE-031 under section S4, prohibited at all times.
Storage
As a large fusion protein, ACE-031 is sensitive to heat and to repeated freezing and thawing. Keep it cold, and do not rely on room temperature through Philippine summers or brownouts. Once mixed, store at 2 to 8°C.
