title: Ataluren treatment of patients with nonsense mutation dystrophinopathy.
abstract: BACKGROUND
  Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled study; males ≥ 5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N=57); ataluren 20, 20, 40 mg/kg (N=60); or placebo (N=57) for 48 weeks. The primary endpoint was change in 6-Minute Walk Distance (6MWD) at Week 48.
  
  
  RESULTS
  Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ=31.3 meters, post hoc P=0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo.
  
  
  CONCLUSIONS
  As the first investigational new drug targeting the underlying cause of nm-dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Katharine
authors.initials: K
authors.lastname: Bushby
authors.forename: Richard
authors.initials: R
authors.lastname: Finkel
authors.forename: Brenda
authors.initials: B
authors.lastname: Wong
authors.forename: Richard
authors.initials: R
authors.lastname: Barohn
authors.forename: Craig
authors.initials: C
authors.lastname: Campbell
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.forename: Anne M
authors.initials: AM
authors.lastname: Connolly
authors.forename: John W
authors.initials: JW
authors.lastname: Day
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Flanigan
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goemans
authors.forename: Kristi J
authors.initials: KJ
authors.lastname: Jones
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mercuri
authors.forename: Ros
authors.initials: R
authors.lastname: Quinlivan
authors.forename: James B
authors.initials: JB
authors.lastname: Renfroe
authors.forename: Barry
authors.initials: B
authors.lastname: Russman
authors.forename: Monique M
authors.initials: MM
authors.lastname: Ryan
authors.forename: Mar
authors.initials: M
authors.lastname: Tulinius
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
authors.forename: H
authors.initials: H
authors.lastname: Lee Sweeney
authors.forename: Richard T
authors.initials: RT
authors.lastname: Abresch
authors.forename: Kim L
authors.initials: KL
authors.lastname: Coleman
authors.forename: Michelle
authors.initials: M
authors.lastname: Eagle
authors.forename: Julaine
authors.initials: J
authors.lastname: Florence
authors.forename: Eduard
authors.initials: E
authors.lastname: Gappmaier
authors.forename: Allan M
authors.initials: AM
authors.lastname: Glanzman
authors.forename: Erik
authors.initials: E
authors.lastname: Henricson
authors.forename: Jay
authors.initials: J
authors.lastname: Barth
authors.forename: Gary L
authors.initials: GL
authors.lastname: Elfring
authors.forename: Allen
authors.initials: A
authors.lastname: Reha
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Spiegel
authors.forename: Michael W
authors.initials: MW
authors.lastname: O'donnell
authors.forename: Stuart W
authors.initials: SW
authors.lastname: Peltz
authors.forename: Craig M
authors.initials: CM
authors.lastname: Mcdonald
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016189:Dystrophin / Q000235:genetics*; D006801:Humans; D007391:International Cooperation; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D017063:Outcome Assessment, Health Care; D010069:Oxadiazoles / Q000627:therapeutic use*; D011446:Prospective Studies; D013997:Time Factors; D016138:Walking
chemical_list: D018389:Codon, Nonsense; D016189:Dystrophin; D010069:Oxadiazoles; C515878:ataluren
keywords: Duchenne muscular dystrophy; genetic; nonsense mutation; orphan; pediatric