Ataluren: A Novel Targeted Therapeutic Approach for the Treatment of Cystic Fibrosis

Abstract

A lethal autosomal recessive genetic disease, cystic fibrosis (CF) is most common in Caucasians and the prevalence varies with the ethnic origin of the population. Patients with CF lack adequate levels of the CF transmembrane conductance receptor (CFTR) protein, a chloride channel necessary for normal function of the lung, pancreas, liver and other organs. Nonsense (premature stop codon) mutations in mRNA for the CFTR cause CF in approximately 10% of patients.  Ataluren, a protein restoration therapy, is designed to promote the translational read-through of premature stop codons that helps to overcome the nonsense mutation and enable the production of a full-length, functional CFTR protein. Insertion of a near cognate amino acid at a premature stop codon allows the protein translation to continue until one of the several stop codons normally present at the ends of mRNA transcript is reached and properly utilized. It is a “corrector” drug specific for type I mutation defects. Ataluren is a novel, orally bioavailable drug that addresses the molecular basis of the disease. Phase III Clinical trials have shown it to be efficacious and well tolerated. It represents a breakthrough in the pharmacological advances for a rare genetic disease.

KEYWORDS: ataluren, non sense mutation, read-through