Targeting cystic fibrosis pathophysiology is changing the future for children worldwide

Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7, most commonly diagnosed at birth via heel prick testing. Patients with CF suffer from a variety of complications including lung disease, gastrointestinal disease and pancreatic dysfunction leading to malabsorption and secondary diabetes mellitus. To date, treatment has been largely symptomatic, but the recent development of a new class of drug, the CFTR modulator, may be a game-changer for children with CF. CFTR modulators target the underlying pathophysiological process of CF itself, either the misfolding of protein channels (correctors) or the length of time functional channels remain open (potentiators). This study aims to review the literature to date on ivacaftor, a CFTR potentiator approved for use in CF patients two years and older with G551D mutation; lumacaftor, a CFTR corrector with as-yet unproven benefit; and, lumacaftor/ivacaftor combination (Orkambi), which shows modest but significant improvement in patients with the F508del mutation, specifically focusing on efficacy, safety profiles and current guidelines.