Ataluren treatment of patients with nonsense mutation dystrophinopathy

Muscle Nerve. 2014 Oct;50(4):477-87. doi: 10.1002/mus.24332.


Introduction: 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.

Keywords: Duchenne muscular dystrophy; genetic; nonsense mutation; orphan; pediatric.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Codon, Nonsense / genetics*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Dystrophin / genetics*
  • Humans
  • International Cooperation
  • Male
  • Muscular Dystrophy, Duchenne / drug therapy*
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / physiopathology
  • Outcome Assessment, Health Care
  • Oxadiazoles / therapeutic use*
  • Prospective Studies
  • Time Factors
  • Walking


  • Codon, Nonsense
  • Dystrophin
  • Oxadiazoles
  • ataluren