Cystic fibrosis: Physiopathology and the latest pharmacological treatments

Abstract

Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease, caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which primarily affects the lungs and digestive system. This gene encodes the CFTR protein, a distinctive membrane transporter of the ATP-binding cassette (ABC) superfamily. It functions as a chloride channel, allowing the balance and transport of chloride through the apical membrane of epithelial cells. Due to its ubiquitous location, mutations in the CFTR gene trigger multiple changes in ion transport and metabolic pathways, affecting various organs, as it will be herein explained. Pulmonary impairment is the most characteristic comorbidity of CF and respiratory failure is the main cause of death. This review presents the importance of an early diagnosis of CF to establish, as soon as possible, a primary therapy for symptomatic prevention and relief. It also mentions new therapeutic approaches that include CFTR modulators. They are correctors and/or potentiators of the deficient CFTR channel. In an attempt to overcome the disadvantages of CFTR modulators, the application of biotechnology techniques is addressed, such as gene therapy, gene editing, RNA therapy and therapeutic microRNAs. The potential of the intranasal administration route is another presented aspect.

Keywords: Amiloride (PubChem CID:16231); Azithromycin (PubChem CID:447043); Aztreonam (PubChem CID:5742832); Benzamil (PubChem CID:108107); Biotechnology; CFTR; CFTR modulators; Cystic fibrosis; Ibuprofen (PubChem CID:3672); Inhalation; Ivacaftor (PubChem CID:16220172); Lumacaftor (PubChem CID:16678941); Phenamil (PubChem CID:135403792); Tezacaftor (PubChem CID:46199646); Tobramycin (PubChem CID:36294).