There are only a relatively limited armoury of drugs, the majority of which are aimed at downstream symptoms of cystic fibrosis. Therapies targeting the basic defect in CF as well as continued availability of more conventional drugs are required. Progress in gene therapy has been limited by the significant barriers to gene transfer of the CF lung, but the UK is hosting a large repeated dose trial of nebulized non-viral gene therapy designed around clinically meaningful outcomes. The UK CF Gene Therapy Consortium is also seeking to develop a promising modified lentiviral approach, although this is some years off. Perhaps the exciting development of recent decades has come from small molecule CFTR modulators, driven by an understanding of basic pathophysiological mechanisms. Ivacaftor is the first drug to be licensed, having proved itself highly clinically efficacious in patients with the class-3 gating mutation G551D. The trial pipeline seeks to expand indications for this and to explore the potential of Phe508del correctors. Finally, a number of anti-inflammatory and anti-infective strategies are being pursued. The emerging global problem of antibiotic resistance is leading to exciting alternatives such as biofilm disruption and bacteriophage to be explored.
Overview of CFTR Modulators and Gene Therapy
