The era of CFTR modulators: improvements made and remaining challenges. Issue 2 (June 2020)

• Record Type: Journal Article
• Authors: Cuevas-Ocaña, Sara; Laselva, Onofrio; Avolio, Julie; Nenna, Raffaella
• Is Part Of: Breathe. Volume 16:Issue 2(2020)
• Publication Date: 2020-06
• Subjects: Respiratory organs -- Diseases; Respiratory organs -- Diseases -- Treatment; Periodicals; 616.2005
• DOI: 10.1183/20734735.0016-2020
• Languages: English
• ISSNs: 1810-6838

Abstract

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator ( CFTR ) gene [1]. The CFTR protein is an ion channel that mediates chloride and bicarbonate transport in epithelial cells of multiple organs including lungs, pancreas and intestine [2, 3]. A defective CFTR protein produces an impaired ion and fluid secretion in the epithelial cells affecting several organs and leading to severe lung disease. More than 2000 CF-causing mutations have been identified [4, 5]. The most common mutation, the deletion of phenylalanine at position 508 (F508del), induces misfolding of the protein that is retained in the endoplasmic reticulum and degraded by proteasomal pathways [6]. The entry into the clinic of CFTR modulators such as TRIKAFTA has significantly improved life for ∼90% CF patients carrying one or two F508del mutations but challenges remain for rare CFTR mutations and the management of lung infections @SaraOcana1 https://bit.ly/3aRafQF