Abstract
Introduction: ACE-031 is a fusion protein of activin receptor type IIB and IgG1-Fc, which binds myostatin and related ligands. It aims to disrupt the inhibitory effect on muscle development and provide potential therapy for myopathies like Duchenne muscular dystrophy (DMD). Methods: ACE-031 was administered subcutaneously every 2–4 weeks to DMD boys in a randomized, double-blind, placebo-controlled, ascending-dose trial. The primary objective was safety evaluation. Secondary objectives included characterization of pharmacokinetics and pharmacodynamics. Results: ACE-031 was not associated with serious or severe adverse events. The study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias. A trend for maintenance of the 6-minute walk test (6MWT) distance in the ACE-031 groups compared with a decline in the placebo group (not statistically significant) was noted, as was a trend for increased lean body mass and bone mineral density (BMD) and reduced fat mass. Conclusion: ACE-031 use demonstrated trends for pharmacodynamic effects on lean mass, fat mass, BMD, and 6MWT. Non–muscle-related adverse events contributed to the decision to discontinue the study. Myostatin inhibition is a promising therapeutic approach for DMD. Muscle Nerve 55: 458–464, 2017.
Original language | English (US) |
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Pages (from-to) | 458-464 |
Number of pages | 7 |
Journal | Muscle and Nerve |
Volume | 55 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1 2017 |
Keywords
- 6-minute walk test
- Duchenne muscular dystrophy
- TGF-β superfamily
- lean body mass
- myostatin inhibitor
- placebo-controlled clinical trial
ASJC Scopus subject areas
- Physiology
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Physiology (medical)