Journal article
Ataluren treatment of patients with nonsense mutation dystrophinopathy
Muscle & nerve, Vol.50(4), pp.477-487
10/2014
DOI: 10.1002/mus.24332
PMCID: PMC4241581
PMID: 25042182
Abstract
ABSTRACT
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. Muscle Nerve 50: 477–487, 2014
Details
- Title: Subtitle
- Ataluren treatment of patients with nonsense mutation dystrophinopathy
- Creators
- Katharine Bushby - Institute of Genetic Medicine, Newcastle UniversityRichard Finkel - The Children's Hospital of PhiladelphiaBrenda Wong - Cincinnati Children's Hospital Medical CenterRichard Barohn - University of Kansas Medical CenterCraig Campbell - University of Western OntarioGiacomo P Comi - University of MilanAnne M Connolly - Washington University School of Medicine at St. LouisJohn W Day - University of MinnesotaKevin M Flanigan - Nationwide Children's Hospital and the Ohio State UniversityNathalie Goemans - University Hospitals LeuvenKristi J Jones - Sydney Children's Hospital Network, and Disciplines of Genetics and Paediatrics and Child Health, Faculty of Medicine University of SydneyEugenio Mercuri - Università Cattolica Sacro CuoreRos Quinlivan - The Institute of NeurologyJames B Renfroe - Northwest Florida Clinical Research GroupBarry Russman - Oregon Health & Science University and Shriners Hospital for ChildrenMonique M Ryan - Royal Children's Hospital, Murdoch Childrens Research Institute and University of MelbourneMar Tulinius - The University of GothenburgThomas Voit - Institut de Myologie, University Pierre et Marie Curie Paris 6Steven A Moore - University of IowaH Lee Sweeney - University of PennsylvaniaRichard T Abresch - UC Davis Children's Hospital, Lawrence J. Ellison Ambulatory Care CenterKim L Coleman - OrthoCare InnovationsMichelle Eagle - Institute of Genetic Medicine, Newcastle UniversityJulaine Florence - Washington University School of Medicine at St. LouisEduard Gappmaier - University of Utah School of MedicineAllan M Glanzman - The Children's Hospital of PhiladelphiaErik Henricson - UC Davis Children's Hospital, Lawrence J. Ellison Ambulatory Care CenterJay Barth - PTC TherapeuticsGary L Elfring - PTC TherapeuticsAllen Reha - PTC TherapeuticsRobert J Spiegel - PTC TherapeuticsMichael W O'donnell - PTC TherapeuticsStuart W Peltz - PTC TherapeuticsCraig M Mcdonald - UC Davis Children's Hospital, Lawrence J. Ellison Ambulatory Care Center
- Resource Type
- Journal article
- Publication Details
- Muscle & nerve, Vol.50(4), pp.477-487
- DOI
- 10.1002/mus.24332
- PMID
- 25042182
- PMCID
- PMC4241581
- NLM abbreviation
- Muscle Nerve
- ISSN
- 0148-639X
- eISSN
- 1097-4598
- Number of pages
- 11
- Language
- English
- Date published
- 10/2014
- Academic Unit
- Pathology
- Record Identifier
- 9984047797302771
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