The Challenges and Promises of New Therapies for Cystic Fibrosis

Abstract

Therapeutic intervention in cystic fibrosis (CF) remains a challenge, partly because of the number of organs and tissues affected by the lack of a functional cystic fibrosis transmembrane conductance regulator (CFTR) protein. CF was originally regarded primarily as a gastrointestinal (GI) disease because of the failure to thrive and early death from malnutrition in infants with CF. However, successful interventions for the GI manifestations of CF have left chronic lung infections as the primary cause of morbidity and mortality. Despite a complex microbiology within the CF lung, one pathogen, Pseudomonas aeruginosa, remains the critical determinant of pulmonary pathology. Treatment and management of this infection and its associated symptoms are the major targets of extant and developing CF therapies. Understanding the multitude of effects of CFTR on mucosal physiology and susceptibility and progression of chronic lung disease, and how host immune responses fail to adequately control lung infection, will be essential for the development of improved therapies for CF.