New and emerging targeted therapies for cystic fibrosis

• Published in: BMJ (Online) 2016-03, Vol.352, p.i859-i859
• Main Authors: Quon, Bradley S, Rowe, Steven M
• Format: Article
• Language: English
• Subjects: Aminophenols - therapeutic use; Aminopyridines - therapeutic use; Antibiotics; Bacterial infections; Benzodioxoles - therapeutic use; Clinical Review; Clinical Trials as Topic; Cystic fibrosis; Cystic Fibrosis - genetics; Cystic Fibrosis - therapy; Cystic Fibrosis Transmembrane Conductance Regulator - drug effects; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - physiology; Drug Discovery - trends; Drug Therapy, Combination; Enzymes; Forced Expiratory Volume - drug effects; Forecasting; Genes; Genetic Therapy - methods; Genetic Therapy - trends; Homozygote; Humans; Inflammation; Kinases; Molecular Targeted Therapy - methods; Molecular Targeted Therapy - trends; Mutation; Mutation - genetics; Nitric oxide; Oxadiazoles - therapeutic use; Phosphodiesterase 5 Inhibitors - therapeutic use; Practice Guidelines as Topic; Precision Medicine - methods; Precision Medicine - trends; Proteins; Quinolones - therapeutic use
• ISSN: 1756-1833; 0959-8138; 1756-1833
• DOI: 10.1136/bmj.i859

Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects about 70 000 people worldwide. The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated understanding of how thousands of mutations in the CFTR gene affect the structure and function of the CFTR protein. Much progress has been made over the past decade with the development of orally bioavailable small molecule drugs that target defective CFTR proteins caused by specific mutations. Furthermore, there is considerable optimism about the prospect of gene replacement or editing therapies to correct all mutations in cystic fibrosis. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This review provides an update on advances in our understanding of the structure and function of the CFTR, with a focus on state of the art targeted drugs that are in development.