ACE-031 (1mg)

ACE-031 is a recombinant fusion protein (~90 kDa) consisting of the extracellular domain of the human ActRIIB (Activin Receptor Type IIB) receptor fused to the Fc portion of human IgG1. It functions as a circulating 'soluble decoy receptor'—it binds free members of the TGF-β superfamily, primarily myostatin (GDF-8), activins A/B, GDF-11, and BMP-9/10, preventing them from binding to membrane-bound ActRIIB receptors. By neutralizing these negative regulators, it releases the brake on skeletal muscle growth. In studies on C57BL/6 mice, 28 days of administration of an ACE-031 analog (RAP-031) increased soleus weight by 28%, plantaris by 44%, and tibialis anterior by 14%. The increase in muscle mass was independent of fiber type (affecting type I & II equally). The Fc-fusion design provides a 10–15 day half-life via FcRn recycling, allowing for weekly or bi-weekly dosing.

• Reconstitution: Add 1.0 mL bacteriostatic water → 1 mg/mL (1000 mcg/mL).
• Typical Dose: 100–250 mcg once weekly or 1 mg every 2 weeks.
• Storage: Lyophilized: −20 °C · reconstituted: 2–8 °C · use within 14 days.

1. Draw 1.0 mL of bacteriostatic water.
2. Inject slowly against the wall · do not spray directly — large protein, sensitive.
3. Gently swirl until fully dissolved — do not shake.
4. Note the date and concentration (1 mg/mL).
5. Refrigerate at 2–8 °C · use within 14 days.

• Objective: Neutralize myostatin, activins, and GDF-11 via a decoy receptor to support muscle growth.
• Schedule: Weekly or bi-weekly subcutaneous injections for 4–8 weeks.
• Unique: Fc-fusion design → 10–15 day half-life (very infrequent dosing).
• Clinical History: Acceleron Pharma studied ACE-031 in Phase 2 for Duchenne Muscular Dystrophy (DMD) but halted it due to vascular side effects.

• Micro-Pulse (Wks 1–2): 100 mcg/wk subcutaneously — initial tolerance assessment.
• Introductory (Wks 3–4): 250 mcg/wk — monitor for blood pressure and epistaxis.
• Standard (Wks 5–8): 500 mcg/wk — main protocol.
• Alternative (full vial): 1 mg every 14 days.
• Washout: 4–8 weeks between cycles.
• Break between cycles: After the cycle (4–8 weeks), a washout period of 4–8 weeks is recommended. The long half-life (10–15 days) means its action continues for ~4 weeks after the last dose.

• Lyophilized: −20 °C in dark, dry conditions · stable for >12 months.
• Reconstituted: Refrigerator 2–8 °C · use within 14 days.
• Do not shake — large fusion protein, sensitive to mechanical stress.

• ⚠️ Clinical trial halted due to vascular side effects (telangiectasias, epistaxis) in DMD patients.
• Monitor blood pressure and vascular symptoms.
• Large protein (~90 kDa) — do not shake during reconstitution.
• Research substance — no FDA/EMA approval.
• In mouse experiments, 4 weeks of administration increased body weight by 16% and significantly increased muscle mass.

1. Soluble Activin Type IIB Receptor Promotes Skeletal Muscle Growth (PMC) — Administration of a soluble activin type IIB receptor promotes skeletal muscle growth — C57BL/6 mice study
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2. ACE-031 Phase 2 Study in Duchenne Muscular Dystrophy — ClinicalTrials.gov — ACE-031 Phase 2 study in Duchenne Muscular Dystrophy (terminated)
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3. Soluble ActRIIB Increases Muscle Mass and Bone Mineral Density in Mice — A soluble form of ActRIIB increases muscle mass and bone mineral density in mice
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4. World of Peptides — ACE-031 protocol, dosage and reconstitution guide
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5. Nature Reviews Drug Discovery — Myostatin and activin blockade by engineered proteins
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