ACE-031
ACE-031 is an investigational protein therapeutic designed to build muscle and increase strength by inhibiting signaling through the activin receptor type IIB (ActRIIB). Research primarily focused on its potential to treat muscle-wasting diseases like Duchenne muscular dystrophy, though clinical trials were halted due to safety concerns involving bleeding.
01Dosing reference
02Mechanism of action
Ligand Binding
ACE-031 acts as a decoy receptor, binding to myostatin and other TGF-beta family proteins in the bloodstream.
Receptor Blockade
By binding these proteins, it prevents them from interacting with the endogenous ActRIIB receptors on muscle cells.
Muscle Growth Disinhibition
Removing the inhibitory signal normally provided by myostatin allows for significant increases in muscle mass and strength.
03Human evidence
Increased lean body mass and thigh muscle volume in healthy postmenopausal women.
Phase 1 double-blind, placebo-controlled study evaluating single and multiple doses; showed dose-dependent increases in muscle mass.
Trends toward maintained muscle function in boys with Duchenne muscular dystrophy, but trials were halted due to adverse events.
Phase 2 dose-escalation study; stopped prematurely due to non-muscle-related side effects including epistaxis and telangiectasias.
04Preclinical evidence
Significant increases in skeletal muscle mass and improved muscle function.
Studies in mdx mice (a model for Duchenne muscular dystrophy) demonstrated enhanced muscle growth and force generation.
Dose-dependent increases in lean body mass in non-human primates.
Cynomolgus monkeys treated with ACE-031 showed substantial muscle hypertrophy without significant changes in fat mass.
05What is known vs. unknown
- ACE-031 is a recombinant fusion protein that acts as a decoy receptor for myostatin and other negative regulators of muscle mass.
- It demonstrated a strong ability to increase lean muscle mass in both animal models and early human trials.
- Clinical development was halted by Acceleron Pharma and Shire due to non-muscle-related adverse events.
- It is banned by the World Anti-Doping Agency (WADA) as a performance-enhancing drug.
- The exact mechanism causing the vascular side effects (nosebleeds, dilated blood vessels) is not fully understood.
- Long-term safety and viability as a therapeutic remain unknown due to the premature termination of clinical trials.
06Safety & regulatory context
07Compared with Follistatin
08Glossary
09Knowledge check
10Sources
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