Chronic ataluren (PTC124) treatment of nonsense mutation cystic fibrosis
Wilschanski M, Miller LL, Shoseyov D et al.
Editor’s note: Diseases such as cystic fibrosis (CF) that are caused by single-gene mutations have different clinical phenotypes, based on the genotype of individual patients. Overall, >1600 mutations in the CF transmembrane conductance regulator gene have been described and grouped based on their effect. Class 1 mutations lead to disruption of the production of full-length, functional proteins. Typically, these mutations are nonsense mutations, leading to premature stop codons that disrupt the ribosomal read-through. The development of potential direct treatments for gene defects in CF that will lead to the production of functional proteins is being intensively studied; such treatments have the potential to change the course of the disease in the future.
Ataluren (PTC124) is an orally bioavailable drug that induces selective ribosomal read-through of mRNA containing a premature stop codon, thereby allowing the translation of full-length protein. In the present study, Wilschanski et al. investigate the effects of long-term ataluren treatment in a group of CF patients with stop mutations.