What is the recommended ACE-031 dosage?

ACE-031 dosing varies by experience level. Beginners typically start at 3000mcg 2x/week, moderate users at 5000mcg 2x/week, and aggressive protocols use 10000mcg 2x/week.

How do you reconstitute ACE-031?

ACE-031 typically comes in 1mg or 2mg or 5mg vials. Add 1mL of bacteriostatic water to the vial. Use our free calculator for exact syringe units based on your desired dose.

What is the half-life of ACE-031?

The half-life of ACE-031 is 10-15 days. This determines how frequently you need to dose for consistent blood levels.

ACE-031

Growth HormoneInjectionResearchGrade C10-15 days half-life

Myostatin InhibitorActRIIBMuscle GrowthFusion ProteinDuchenne Muscular DystrophyLigand TrapTGF-BetaDiscontinuedLean Mass12 weeks on / 10 weeks off

Benefits

Demonstrated statistically significant increases in lean body mass in both healthy adults and DMD patients

Single injection at 3 mg/kg produced 3.3% total lean mass gain and 5.1% thigh muscle volume increase in 29 days

Long half-life (10-15 days) permits infrequent dosing — every 2-4 weeks

Improved bone mineral density markers in the Phase 2 DMD trial

Preclinical efficacy across multiple muscle-wasting models (ALS, DMD, glucocorticoid-induced, sarcopenia)

Up to 19% increase in lean body mass in preclinical glucocorticoid-induced muscle loss models

Linear pharmacokinetics across all tested doses

Half-Life

10-15 days

Route

Injection

Frequency

2x/week

Vial Sizes

1mg, 2mg, 5mg

BAC Water

1mL

Safety Grade

Grade C

Open ACE-031 Dosage Calculator

Calculate exact syringe units for your vial and dose

About ACE-031

ACE-031 is a recombinant fusion protein designed to act as a decoy receptor for myostatin and related ligands in the TGF-beta superfamily. It consists of the extracellular domain of the activin type IIB receptor (ActRIIB) fused to the Fc portion of human IgG1, which extends its circulating half-life and allows for subcutaneous dosing every 2-4 weeks. The biological rationale behind ACE-031 is straightforward. Myostatin is the primary negative regulator of skeletal muscle growth. Animals and humans with naturally occurring myostatin mutations develop pronounced muscular hypertrophy. By flooding the extracellular space with a soluble version of myostatin's receptor, ACE-031 intercepts the ligand before it can bind the membrane-bound receptor and activate its downstream signaling cascade (Smad2/3 phosphorylation), effectively removing the brake on muscle protein synthesis. The problem is that ActRIIB doesn't bind only myostatin. It also captures activin A, activin B, GDF-11, and critically, BMP-9 and BMP-10. Those last two ligands are essential for maintaining vascular endothelial integrity. When ACE-031 sequesters BMP-9 and BMP-10, it destabilizes endothelial cells, leading to the formation of telangiectasias (small dilated blood vessels in the skin) and epistaxis (nosebleeds). This is the mechanism that ended the clinical program. In the Phase 1 single ascending-dose study, 48 healthy postmenopausal women received a single injection of ACE-031 at doses ranging from 0.02 to 3 mg/kg. At the highest dose, participants gained a mean 3.3% total body lean mass and 5.1% thigh muscle volume by day 29 — from a single injection. Pharmacokinetics were linear across all doses, with a half-life of 10-15 days. The Phase 2 trial enrolled ambulatory boys with DMD ages 4-16. Cohort 2 showed a statistically significant 5.2% increase in total body lean mass versus 2.6% in the placebo group. Bone mineral density markers also improved. However, the trial was terminated before enrolling additional cohorts due to epistaxis and telangiectasias at doses in the 1.0-2.5 mg/kg range. ACE-031 remains an important proof of concept for myostatin inhibition as a therapeutic strategy. Subsequent programs (like ACE-2494 and bimagrumab) attempted to refine the ligand selectivity to avoid the BMP-9/10 trap.

Who Should Consider ACE-031

Researchers studying myostatin and TGF-beta superfamily signaling in muscle physiology
Muscle-wasting disease researchers — ACE-031 demonstrated measurable lean mass gains in DMD patients
Scientists investigating sarcopenia and age-related muscle loss interventions
Body composition researchers — Phase 1 showed 3.3% lean mass gain from a single injection

How ACE-031 Works

ACE-031 functions as a ligand trap — a soluble decoy receptor that intercepts signaling molecules before they can reach their membrane-bound targets. The molecule consists of the extracellular domain of activin receptor type IIB (ActRIIB) fused to a human IgG1 Fc fragment. This design exploits the natural ligand-binding properties of ActRIIB while adding the stability and extended half-life conferred by the Fc region. The primary intended target is myostatin (GDF-8), the dominant negative regulator of skeletal muscle mass. Under normal physiology, myostatin binds to membrane-bound ActRIIB, recruits the type I receptor ALK4 or ALK5, and triggers phosphorylation of Smad2 and Smad3. These phosphorylated Smads complex with Smad4 and translocate to the nucleus, where they suppress genes involved in muscle protein synthesis and activate genes driving muscle protein degradation (including the ubiquitin-proteasome pathway components MuRF1 and MAFbx/atrogin-1). By capturing myostatin in the extracellular space, ACE-031 prevents this entire anti-anabolic cascade from initiating. However, ActRIIB is a promiscuous receptor. ACE-031 also binds activin A, activin B, GDF-11, and members of the bone morphogenetic protein (BMP) family — particularly BMP-9 and BMP-10. The sequestration of activins and GDF-11 likely contributes to the muscle-building and bone density effects. But the capture of BMP-9 and BMP-10 proved to be the molecule's downfall. These ligands signal through ALK1 on endothelial cells and are essential for maintaining vascular stability. When ACE-031 removes BMP-9/10 from circulation, endothelial cells lose a critical survival signal, leading to telangiectasias and epistaxis. The FSH reduction observed in healthy women at 3 mg/kg reflects activin A sequestration. Activin A is a key stimulator of pituitary FSH secretion, so trapping it predictably suppresses FSH output.

What to Expect

Weeks 1-2

Based on Phase 1 data, initial increases in lean body mass may begin within the first two weeks following administration. Pharmacokinetic steady state has not yet been reached.

Weeks 3-6

Lean mass gains become measurable by DXA. In the Phase 1 study, peak lean mass increase (3.3%) was observed by day 29 after a single 3 mg/kg dose. Bone mineral density markers may begin to shift.

Weeks 8-12

With repeated dosing (as in the Phase 2 trial), lean mass gains of approximately 5% are possible. Vascular adverse events (telangiectasias, epistaxis) may emerge during this window, particularly at doses of 1 mg/kg or above given biweekly.

Dosing Protocol

Level	Dose / Injection	Frequency
Beginner	3mg	2x/week
Moderate	5mg	2x/week
Aggressive	10mg	2x/week

Note: ACE-031 is a soluble activin receptor type IIB (ActRIIB) decoy receptor — a fusion protein combining the extracellular domain of ActRIIB with a human IgG1 Fc fragment. Developed by Acceleron Pharma for Duchenne muscular dystrophy. Clinical development halted in April 2011 after vascular safety signals (epistaxis and telangiectasias) emerged during the Phase 2 DMD trial. These events were attributed to off-target inhibition of BMP-9 and BMP-10. All adverse events resolved upon discontinuation.

How to Inject ACE-031

Add bacteriostatic water slowly along the vial wall to avoid denaturing the fusion protein. For a 1 mg vial with 1 mL BAC water, each 0.1 mL delivers 0.1 mg. Swirl gently until dissolved — do not shake or vortex. Inject subcutaneously into the abdominal area, upper thigh, or upper arm. Rotate injection sites. Use a 29-31 gauge insulin syringe. Given the biweekly dosing schedule, site rotation is straightforward. No specific timing requirements were established in clinical trials.

Cycling Protocol

On Period

12 weeks

Off Period

10 weeks

The Phase 2 DMD trial used a 12-week treatment period. No established cycling protocol exists for research use outside clinical trials. Extended use is not recommended given the known vascular safety signals. Periodic monitoring for telangiectasias, epistaxis, and gum bleeding should be performed throughout any research protocol.

Pharmacokinetics

Half-Life

300h

Bioavailability

SC: not formally reported but dose-proportional systemic exposure across all tested doses (0.02-3 mg/kg) in Phase 1

Tmax

Not publicly reported; lean mass effects peaked at approximately day 29 post-injection

Data Confidence

moderate

Source: Half-life of 10-15 days (~240-360 hours) based on Phase 1 single ascending-dose study in healthy postmenopausal women at 3 mg/kg (Attie et al. 2013, PMID 23169607). Linear pharmacokinetics across all tested doses.

Pharmacokinetics — Active Dose Over Time

Loading the interactive decay curve.

Side Effects

The most clinically relevant adverse events were epistaxis (nosebleeds) and telangiectasias (small dilated blood vessels visible on the skin). These vascular effects emerged during the Phase 2 DMD trial at doses of 1.0-2.5 mg/kg given every two weeks, attributed to off-target inhibition of BMP-9 and BMP-10. All vascular events resolved completely upon drug discontinuation, and no serious or severe adverse events were reported. Additional findings included minor gum bleeding, erythema, and a 43% reduction in serum FSH in healthy postmenopausal women at 3 mg/kg. Injection site reactions were mild. Long-term safety profile has never been characterized due to halted clinical development.

Contraindications

Hereditary hemorrhagic telangiectasia (HHT) or any vascular fragility syndrome — ACE-031 inhibits BMP-9/10 signaling critical for vascular integrity
Active bleeding disorders or concurrent anticoagulant therapy — the compound caused epistaxis and gum bleeding in clinical trials
Pregnancy and breastfeeding — no reproductive safety data exists, and FSH suppression was observed in healthy women
Individuals under 18 outside supervised clinical research — pediatric safety data is limited to the halted DMD trial
Known hypersensitivity to ACE-031 or any Fc-fusion protein
Pulmonary arterial hypertension — BMP-9/10 signaling disruption may worsen pulmonary vascular disease

Drug Interactions

Anticoagulants (warfarin, heparin, DOACs) — ACE-031 caused epistaxis and gum bleeding through BMP-9/10 inhibition; concurrent use may amplify bleeding risk
Other myostatin inhibitors (follistatin, bimagrumab) — combining multiple myostatin-pathway inhibitors could produce unpredictable effects; no co-administration data exists
Hormonal contraceptives / fertility treatments — ACE-031 caused a 43% decrease in FSH through activin A sequestration; may interfere with these therapies
TGF-beta pathway modulators (luspatercept, sotatercept) — overlapping ligand pathways; co-administration could result in excessive TGF-beta superfamily inhibition
Growth Hormone / IGF-1 therapies — potential additive anabolic effects; no interaction data exists