Ivacaftor: a novel gene-based therapeutic approach for cystic fibrosis

Abstract

Ivacaftor is a new therapeutic agent that acts at the cystic fibrosis transmembrane conductance regulator (CFTR) channel to alter activity. It is approved for use in patients 6 years and older with cystic fibrosis who have at least 1 G551D mutation in the CFTR gene. It is unlike any other current pharmacologic agent for cystic fibrosis in that it specifically targets the gene defect associated with cystic fibrosis as opposed to treating resulting symptomology. Mucoactive agents, antibiotics, inhaled beta agonists, and other anti-inflammatory agents are currently the mainstay of cystic fibrosis treatment but can be associated with several side effects in addition to cumbersome frequency of administration. Ivacaftor's oral dosing regimen offers a more convenient treatment option. However, it is associated with significant drug-drug interactions.

Keywords: CFTR; cystic fibrosis; ivacaftor.

Figure.

Classes of CFTR mutations. Class I and II mutations result in CFTR protein that does not reach the cell surface due to impaired protein translation in the cell nucleus (Class I) or misfolded protein in the golgi apparatus (Class II). Class III and IV mutations result in CFTR that reaches the cell surface but exhibits impaired function due to a gating defect (Class III) or decrease conductivity (Class IV). Class V mutations lead to a reduced production of normal CFTR. CFTR, cystic fibrosis transmembrane conductance regulator.