MYOSTATIN INHIBITOR ACE-031 TREATMENT OF AMBULATORY BOYS WITH DUCHENNE MUSCULAR DYSTROPHY: RESULTS OF A RANDOMIZED, PLACEBO- CONTROLLED CLINICAL TRIAL

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.