title: A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy.
abstract: OBJECTIVE
  Myostatin is an endogenous negative regulator of muscle growth and a novel target for muscle diseases. We conducted a safety trial of a neutralizing antibody to myostatin, MYO-029, in adult muscular dystrophies (Becker muscular dystrophy, facioscapulohumeral dystrophy, and limb-girdle muscular dystrophy).
  
  
  METHODS
  This double-blind, placebo-controlled, multinational, randomized study included 116 subjects divided into sequential dose-escalation cohorts, each receiving MYO-029 or placebo (Cohort 1 at 1 mg/kg; Cohort 2 at 3 mg/kg; Cohort 3 at 10 mg/kg; Cohort 4 at 30 mg/kg). Safety and adverse events were assessed by reported signs and symptoms, as well as by physical examinations, laboratory results, echocardiograms, electrocardiograms, and in subjects with facioscapulohumeral dystrophy, funduscopic and audiometry examinations. Biological activity of MYO-029 was assessed through manual muscle testing, quantitative muscle testing, timed function tests, subject-reported outcomes, magnetic resonance imaging studies, dual-energy radiographic absorptiometry studies, and muscle biopsy.
  
  
  RESULTS
  MYO-029 had good safety and tolerability with the exception of cutaneous hypersensitivity at the 10 and 30 mg/kg doses. There were no improvements noted in exploratory end points of muscle strength or function, but the study was not powered to look for efficacy. Importantly, bioactivity of MYO-029 was supported by a trend in a limited number of subjects toward increased muscle size using dual-energy radiographic absorptiometry and muscle histology.
  
  
  CONCLUSIONS
  This trial supports the hypothesis that systemic administration of myostatin inhibitors provides an adequate safety margin for clinical studies. Further evaluation of more potent myostatin inhibitors for stimulating muscle growth in muscular dystrophy should be considered.
authors.affiliation: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-7519, USA. kwagner@jhmi.edu
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Wagner
authors.forename: James L
authors.initials: JL
authors.lastname: Fleckenstein
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Amato
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Barohn
authors.forename: Katharine
authors.initials: K
authors.lastname: Bushby
authors.forename: Diana M
authors.initials: DM
authors.lastname: Escolar
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Flanigan
authors.forename: Alan
authors.initials: A
authors.lastname: Pestronk
authors.forename: Rabi
authors.initials: R
authors.lastname: Tawil
authors.forename: Gil I
authors.initials: GI
authors.lastname: Wolfe
authors.forename: Michelle
authors.initials: M
authors.lastname: Eagle
authors.forename: Julaine M
authors.initials: JM
authors.lastname: Florence
authors.forename: Wendy M
authors.initials: WM
authors.lastname: King
authors.forename: Shree
authors.initials: S
authors.lastname: Pandya
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Paul
authors.initials: P
authors.lastname: Juneau
authors.forename: Kathleen
authors.initials: K
authors.lastname: Meyers
authors.forename: Cristina
authors.initials: C
authors.lastname: Csimma
authors.forename: Tracey
authors.initials: T
authors.lastname: Araujo
authors.forename: Robert
authors.initials: R
authors.lastname: Allen
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Parsons
authors.forename: John M
authors.initials: JM
authors.lastname: Wozney
authors.forename: Edward R
authors.initials: ER
authors.lastname: Lavallie
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Mendell
mesh_terms: D000328:Adult; D000906:Antibodies / Q000627:therapeutic use*; D015331:Cohort Studies; D015897:Comorbidity; D004311:Double-Blind Method; D003875:Drug Eruptions / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D038622:Internationality; D008297:Male; D009136:Muscular Dystrophies / Q000188:drug therapy* / Q000453:epidemiology*; D015990:Placebo Effect; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; C506829:Stamulumab