What Is ACE-031?

1. How does ACE-031 work?

Myostatin, also known as GDF8, is a protein that muscle makes to cap its own growth. It belongs to the TGF-β family, along with activin A and GDF11, and these proteins send their signal by attaching to activin type II receptors on muscle cells, chiefly the IIB form (ActRIIB). ACE-031 is a free-floating version of the receptor’s binding end, so it captures those proteins in the bloodstream before they reach the real receptor (Attie and colleagues’ healthy-volunteer study).

The antibody Fc portion pairs two receptor chains into one molecule and lets it persist in the blood far longer (Reichel and colleagues’ anti-doping analysis). That long-acting design is why ACE-031 works on muscles everywhere at once rather than in one spot.

Why a receptor decoy blocks more than myostatin

The case for the approach came from mice. In Lee and colleagues’ 2005 experiments, a soluble ActRIIB protein enlarged muscles by as much as 60% within two weeks in normal mice. It still produced growth, though less, in mice that had no myostatin at all, which meant other signals using the same receptor were also holding muscle back.

That breadth is the defining feature of ACE-031. A myostatin-only antibody leaves those other signals untouched, while a receptor decoy captures several at once. As section 4 explains, the extra reach likely included a signal that matters for blood vessels.

What the animal studies showed

These results come from animals, not people:

The marmoset study is small, and its authors acknowledge that four control animals limited statistical power. It nonetheless matters as primate evidence that the extra muscle produced more force, something the human trials did not clearly show.

2. How is ACE-031 different from ACE-083 and follistatin?

Acceleron followed ACE-031 with ACE-083, which pursued the same muscle goal with a molecule meant to stay where it was injected. The two drugs failed for different reasons, which is the most useful thing to know when comparing them.

Sources: Attie and colleagues, Campbell and colleagues’ Duchenne trial and Acceleron’s March 2020 announcement on ACE-083.

Follistatin-344 is a third route: a natural binding protein for myostatin and activins, studied in people only as gene therapy. None of the three has an approved use, and results from one cannot be borrowed for another.

3. What did the human trials of ACE-031 find?

Only two human studies have been published. Neither enrolled men without muscle disease, athletes or people losing weight.

One dose in healthy postmenopausal women

Attie and colleagues randomized 48 healthy postmenopausal women 3:1 to a single subcutaneous injection of ACE-031, from 0.02 to 3 mg/kg, or placebo (NCT00755638). The highest dose produced these changes by day 29:

The authors also reported significant shifts in blood markers they read as favorable for bone and fat metabolism. A follow-up multiple-dose study in 70 healthy postmenopausal women finished in 2011, but its results were never posted or published (NCT00952887).

Boys with Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is an inherited disease in which the muscle protein dystrophin is missing and muscle steadily breaks down. The phase 2 trial enrolled walking boys aged 4 or older who had used corticosteroids for at least a year, treated each dose group for 12 weeks and followed them for 12 more (Campbell and colleagues). A planned third dose group never enrolled because the study stopped after the second.

Registry results about 24 weeks after the start (NCT01099761):

The published paper calls these trends: walking distance held steady while the older placebo boys declined, and lean mass and bone density tended to rise. None of it reached statistical significance. With six boys on placebo, wide spreads and children who gain lean mass simply by growing, the table cannot show that ACE-031 improved function, and hand-held strength tests did not consistently favor the drug.

4. Why was ACE-031 stopped?

The trial ended over vascular effects. The registry lists these adverse events (NCT01099761):

Telangiectasias are small dilated blood vessels that become visible in the skin. Campbell and colleagues describe the events as neither serious nor severe, but say these effects outside muscle contributed to stopping the drug. The open-label extension in 11 boys was terminated on the same safety grounds (NCT01239758).

The BMP9 explanation

Acceleron’s later research points to bone morphogenetic protein 9 (BMP9), a signal involved in regulating blood vessels. Li and colleagues reported that the two-armed ActRIIB-Fc design traps BMP9 and altered vessel growth in a mouse retina test, and they engineered a successor molecule specifically to avoid binding it. Former Acceleron scientists have since attributed ACE-031’s vascular effects to its blocking of signals beyond myostatin and activin A, BMP9 in particular (Cadena and colleagues, 2026). This is the developer’s interpretation from animal and laboratory work; no human study has tested it directly.

A related approved drug shows the same pattern

Sotatercept (Winrevair), a related activin receptor IIA-Fc protein approved for pulmonary arterial hypertension, carries the same kinds of effects on its label. In its STELLAR trial, nosebleeds occurred in 22.1% of treated patients versus 1.9% on placebo, and telangiectasia in 16.6% versus 4.4% (Winrevair prescribing information). It is a different molecule for a different disease, but it shows the vascular signal is a known feature of this drug family rather than a one-off.

5. Is ACE-031 approved or legal?

No regulator anywhere received a marketing application for ACE-031. Its path, from the registry and Acceleron’s filings:

Acceleron’s 2013 prospectus says that after further animal toxicology data, the partners judged the risk-benefit balance wrong for young boys with a muscle-wasting disease, and that Acceleron had no plans to resume development.

• United States. As a protein rather than an anabolic steroid, ACE-031 is absent from the Schedule III list (21 CFR 1308.13). Not being scheduled does not make it an approved or legally marketed medicine.
• Sport. The WADA 2026 Prohibited List gives ACE-031 as its example of a decoy activin receptor under S4.3, agents preventing activin receptor IIB activation. These are non-Specified substances, banned in and out of competition. Follistatin falls in the same class.

6. What doses were studied, and how long does ACE-031 last?

There is no approved dose. The only human doses come from the trials and describe research exposure under medical supervision, not a regimen anyone has validated:

In the single-dose study, blood exposure rose in proportion to dose and the mean elimination half-life was 10–15 days. Half-life is the time for the blood level to fall by half, so a long one explains the two- and four-week dosing gaps in the DMD trial. It also means that when an unwanted effect appears, the drug is still present for weeks.

The higher DMD dose, 1.0 mg/kg every two weeks, was the one at which most nosebleeds and telangiectasias appeared. No human data exist beyond 12 weeks of dosing.

7. What is in products sold online as ACE-031?

With the drug abandoned, anything sold under the name today does not come from Acceleron’s program. Reichel and colleagues bought 14 products labeled ACE-031 from online sellers in Britain, mainland Europe, China and the US, each marked for research only or not for human use:

Clinical biologics like ACE-031 are made in mammalian cells, and the full-length receptor found in these vials includes membrane-anchoring parts the drug deliberately lacks. Whatever effect such material has in people is unknown, and the trial data above do not apply to it.

The researchers showed that a doping test they already used for luspatercept, a related ActRIIB-Fc medicine, also flags this counterfeit material. After a 10 mg/kg dose in rats, the material could be found in blood at 48 hours but no longer at day 7; the authors warn that the window in humans may not match.

8. Could ACE-031 help preserve muscle on a GLP-1?

No study has tested ACE-031 with semaglutide, tirzepatide or any other weight-loss drug. There is no evidence on whether it would protect lean mass during a calorie deficit, and no data on interactions. The concern behind the question is real, and the GLP-1 muscle loss guide explains what trials measure, but ACE-031 has no tested answer to offer.

Three facts from the ACE-031 record are worth keeping in mind. The human lean-mass gain was modest and measured after a single dose. In the only multi-dose human trial, gains in lean mass did not clearly translate into better walking or strength. And the drug’s whole-body reach is what produced the vascular effects that ended it.

What can actually be measured

The ACE-031 trials offer a template for what is meaningful to measure in muscle research: lean mass by DXA, muscle volume by MRI, bone density, timed walking tests and measured strength at specific joints. Those are clinician-interpretable outcomes. A bathroom scale or mirror cannot separate muscle from water or fat.

Because the safety signal was vascular, the events that ended the trial, nosebleeds and visible dilated skin vessels, are the observations a clinician would most want dated and recorded. None of the sources reviewed here report reproductive hormone or fertility outcomes for ACE-031, so nothing can be said about those.

A personal log cannot confirm what a vial contained, and the testing above suggests vials sold as ACE-031 usually contain something else. What a log can do is keep dates, products, body-composition readings, strength numbers and symptoms in one timeline a clinician can review. The half-life tracking guide explains why a 10–15 day half-life means effects and side effects can lag well behind the date of a dose.

9. ACE-031 FAQ

• Is ACE-031 the same as ramatercept?

  Yes. Ramatercept is the international nonproprietary name for ACE-031, the activin receptor IIB-Fc fusion protein developed by Acceleron Pharma. Trial registries also call it ActRIIB-IgG1.

• Why was ACE-031 discontinued?

  A placebo-controlled trial in boys with Duchenne muscular dystrophy was stopped in 2011 after nosebleeds and telangiectasias appeared in treated boys. After reviewing further animal toxicology data, Acceleron and Shire concluded in 2013 that the risk-benefit balance did not suit the intended patients.

• Is ACE-031 legal?

  It was never approved as a medicine in any country. In the US it is a protein, not an anabolic steroid, and is not on the Schedule III list, but that does not make it an approved drug. WADA prohibits it by name at all times.

• What are the side effects of ACE-031?

  In the Duchenne trial, nosebleeds and telangiectasias (small dilated blood vessels in the skin) each occurred in 5 of 9 boys at the higher dose and in none on placebo. Injection-site redness and headache were also reported. No serious adverse events were recorded, but the vascular effects helped end development.

• How long does ACE-031 stay in your system?

  In healthy postmenopausal women, the mean elimination half-life after one injection was 10–15 days. That means the drug remains in the body for weeks, including after side effects appear.

• Does ACE-031 build muscle?

  In people, a single high dose produced modest lean-mass and thigh-volume gains over four weeks in healthy older women. Animal studies showed larger gains. No trial has studied healthy men, athletes or strength in healthy people.

• Can ACE-031 be used with semaglutide or tirzepatide to keep muscle?

  No study has tested that combination, so there is no evidence on added muscle retention or on interactions. ACE-031 is also not available as a medicine, and products sold under its name did not contain it when tested.

• Is ACE-031 the same as ACE-083?

  No. Both came from Acceleron and target muscle-limiting signals, but ACE-031 is built from the activin IIB receptor and acts throughout the body, while ACE-083 is a follistatin-based protein designed to act in the injected muscle. ACE-031 was stopped for safety; ACE-083 was stopped because muscle growth did not improve function.

10. Sources