ACE 031

ACE-031 is a fusion protein comprised of the extracellular domain of the human ActRIIB linked to the Fc (hinge CH2 and CH3 domains) portion of the human immunoglobulin G1 (IgG1). ACE-031 binds avidly to myostatin and other negative regulators of muscle mass and inhibits their biological effects by preventing signaling through the endogenous receptor[1].

ACE 031 is a muscle modulator that combines with myostatin and other negative regulators of muscle mass to promote muscle growth. It is a fusion protein of activin receptor type IIB (ActRIIB) and IgG1-Fc that binds to myostatin and related ligands. Clinical studies have shown that ACE 031 can be used to treat myopathies such as Duchenne muscular dystrophy (DMD).

ACE-031, a soluble ACVR2B receptor, was prematurely terminated due to severe adverse effects, including nosebleeds, gum bleeding, telangiectasia, and erythema attributed to cross-inhibition of BMP9 and BMP10, ligands involved in endothelial cell function. In addition, a 43% decrease in serum follicle-stimulating hormone (FSH), whose synthesis is stimulated by activins, was observed in healthy, postmenopausal women who received a single dose (3 mg/kg) of ACE-031, which caused a near-maximal suppression of activin signaling[2].

Ramatercept (ACE-031) is a soluble form of ACVR2B developed by Acceleron Pharma to treat Duchenne Muscular Dystrophy (DMD). Despite encouraging results of both the animal study, in which ACE-031 significantly increased both type 1 and type 2 muscle fiber cross-sectional area in young mice, and phase 1 clinical study in healthy postmenopausal women, in which ACE-031 injection (3 mg/kg) significantly increased total body lean mass and thigh muscle volume, subsequent phase 2 clinical trial in patients with DMD was terminated due to occurrence of non-muscle-related severe adverse events including nosebleed, gum bleeding, telangiectasia, and/or erythema, halting further development of the drug[2].

[1] Craig Campbell. “Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial.” Muscle & Nerve 55 4 (2017): 458–464.
[2] Joonho Suh, Yun-Sil Lee. “Myostatin Inhibitors: Panacea or Predicament for Musculoskeletal Disorders?” Journal of Bone Metabolism 27 3 (2020): 151–165.