title: Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Pediatrics, Epidemiology and Clinical Neurological Sciences, Western University, London, Ontario, Canada.
authors.forename: Craig
authors.initials: C
authors.lastname: Campbell
authors.affiliation: Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: McMillan
authors.affiliation: Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jean K
authors.initials: JK
authors.lastname: Mah
authors.affiliation: McMaster University Medical Centre, Hamilton, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Tarnopolsky
authors.affiliation: British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Selby
authors.affiliation: Acceleron Pharma, Cambridge, Massachusetts, USA.
authors.forename: Ty
authors.initials: T
authors.lastname: McClure
authors.affiliation: Acceleron Pharma, Cambridge, Massachusetts, USA.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Wilson
authors.affiliation: Acceleron Pharma, Cambridge, Massachusetts, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Sherman
authors.affiliation: Kennedy Krieger Institute, Johns Hopkins Medical School, Baltimore, Maryland, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Escolar
authors.affiliation: Acceleron Pharma, Cambridge, Massachusetts, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Attie
mesh_terms: D030301:Activin Receptors, Type II / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000293:Adolescent; D001823:Body Composition / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000000981:diagnostic imaging / Q000188:drug therapy*; D055435:Myostatin / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology
chemical_list: D055435:Myostatin; C579679:ACVR2B protein, human; D030301:Activin Receptors, Type II
keywords: 6-minute walk test; Duchenne muscular dystrophy; TGF-β superfamily; lean body mass; myostatin inhibitor; placebo-controlled clinical trial