ACE 031

Research Focus and Findings

Research on ACE-031 has primarily focused on its potential as a therapy for neuromuscular diseases where muscle loss is a key feature. 

• Muscle Growth: In both animal models (mice, rats, marmosets) and human clinical trials, ACE-031 administration resulted in significant increases in total body lean mass and muscle volume.
• Bone and Fat Metabolism: Studies in postmenopausal women and Duchenne muscular dystrophy boys also indicated that ACE-031 treatment led to trends for improved bone mineral density (BMD) and reduced fat mass.
• Function: In studies with Duchenne muscular dystrophy patients, there were trends for maintaining physical function, such as the 6-minute walk test distance, compared to a decline in placebo groups. 

Clinical Trial Status and Safety Concerns

Clinical trials for ACE-031 in humans were terminated or suspended due to non-muscle-related safety concerns. 

• Adverse Events: Participants in some studies experienced side effects including minor nosebleeds (epistaxis), gum bleeding, and the appearance of small dilated blood vessels in the skin (telangiectasias).
• Reason for Termination: These bleeding events were likely caused by the unintended inhibition of bone morphogenetic protein 9 (BMP9), a ligand important for vascular remodeling, which was also trapped by the ACE-031 decoy receptor. 

Following these events, the companies involved (Acceleron Pharma and Shire) stopped clinical studies of ACE-031 to better understand the safety data. The pathway for myostatin inhibition as a therapeutic approach remains promising, but subsequent research has shifted towards developing more specific inhibitors, like KER-065, that do not have the same effect on BMP9.