ataluren for treating Duchenne muscular dystrophy with a nonsense mutation in the dystrophin gene

Last edited 02/2023 and last reviewed 02/2023

Ataluren for treating Duchenne muscular dystrophy with a nonsense mutation in the dystrophin gene

• Ataluren is recommended, within its marketing authorisation, as an option for treating Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene in people 2 years and over who can walk. This is only if the company provides ataluren according to the commercial arrangement (1)
  • the NICE committee stated
    • ...Duchenne muscular dystrophy, with a nonsense mutation in the dystrophic gene, is a rare and progressive condition. Over time it causes muscle weakness resulting in the loss of the ability to walk and reductions in respiratory ability, and it significantly reduces life expectancy....
    • evidence provided, along with feedback from clinicians and people with the condition, suggests that ataluren is likely to slow down disease progression and delay the loss of the ability to walk. Evidence for improvements in later stages of the disease and improved survival with ataluren is limited and highly uncertain but ataluren may also improve outcomes once the ability to walk has been lost..."
      
      
• Ataluren is a first-in-class, oral treatment for patients with nonsense mutation Duchenne Muscular Dystrophy (nmDMD), designed to enable full-length dystrophin protein production (2)
  • approximately 10-15% of patients with DMD have the disease owing to a nonsense mutation in the DMD gene
  • a nonsense mutation results in a premature stop codon in the protein-coding region of the mRNA
  • Ataluren is a small molecule that is designed to enable the ribosome to read through a premature stop codon in the mRNA so that translation continues as normal, although with reduced efficiency, resulting in the production of a full-length dystrophin protein (3)
    • by restoring the production of dystrophin, treatment with ataluren helps to preserve muscle mass and prolong function in patients with nmDMD

Reference:

• NICE (February 2023). Ataluren for treating Duchenne muscular dystrophy with a nonsense mutation in the dystrophin gene
• Morkous SS. Treatment with Ataluren for Duchene Muscular Dystrophy. Pediatr Neurol Briefs. 2020 Dec 4;34:12.
• McDonald CM, Muntoni F, Penematsa V, Jiang J, Kristensen A, Bibbiani F, Goodwin E, Gordish-Dressman H, Morgenroth L, Werner C, Li J, Able R, Trifillis P, Tulinius M; Study 019 investigators. Ataluren delays loss of ambulation and respiratory decline in nonsense mutation Duchenne muscular dystrophy patients. J Comp Eff Res. 2022 Feb;11(3):139-155.