Protein repair: Cusp of a new era in cystic fibrosis

Cystic fibrosis (CF) is a genetic disease caused by a variety of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which leads to either an absent or a dysfunctional CFTR protein. The specific mechanism of protein dysfunction is dependent on the specific underlying mutation, but can be broadly defined into 5 functional classes. Recent advances in CF therapeutics have focused on the development of drugs targeting the underlying CFTR protein defect to treat the disease (CFTR modulators). In particular, ivacaftor has successfully shown improvements in a subset of CF patients on a variety of clinical outcomes, including a >10% absolute improvement in forced expiratory volume in 1 second. Ivacaftor is the first CFTR modulator approved for the treatment of CF, but its approved indications cover <5% of the CF patients in the United States. However, other drugs are in development, which provide benefit to the >90% of the CF patients with mutations not presently covered by ivacaftor. ©