A Young Hispanic with c.1646G>A Mutation Exhibits Severe Cystic Fibrosis Lung Disease: Is Ivacaftor an Option for Therapy?

Abstract

compelling basic science and animal model observations would provide a solid foundation upon which to implement additional trials of "anti-coagulants" in IPF. In conclusion, we have answered the question of the utility of warfarin in progressive IPF, but many questions remain.

Lumacaftor/ivacaftor combination for cystic fibrosis patients homozygous for Phe508del-CFTR

“…In addition to its potentiating effect on Gly551Asp, ivacaftor also augmented the channel function of a panel of other Class III and IV mutations including Arg117His, Ser549Asn, Ser549Arg, Gly551Ser, Gly970Arg etc. (30-32). …”

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for Ivacaftor Therapy in the Context of CFTR Genotype

“…Speculatively, ivacaftor may be effective in combination with a suppressor in patients with CFTR variants that affect biosynthesis of CFTR (i.e., resulting in premature termination codons) 24 . Individuals with CFTR variants other than G551D‐CFTR that also have a similar gating defect may respond to ivacaftor treatment; however, currently the only published studies addressing this aspect are based on in vitro models 24 , 32 , 34 ( Supplementary Table S4 online). Several clinical trials that aim to evaluate the use of ivacaftor in patients with other CFTR variants are currently under way or are recruiting participants.…”

Capturing the Direct Binding of CFTR Correctors to CFTR by Using Click Chemistry

“…CF is caused by mutations in the gene encoding an ion-channel protein, the CF transmembrane conductance regulator (CFTR). [1] CFTR is predominantly expressed at the apical plasma membrane of epithelial cells lining several organs and functions as a cAMP-regulated chloride/bicarbonate channel. [2] Mutations in the CFTR gene may cause defects in protein synthesis, processing, and trafficking and channel gating/conductance, consequently affecting CFTR-mediated transepithelial chloride and fluid homeostasis.…”

“…[3] Clinically, CFTR dysfunction causes CF lung disease, gastrointestinal disorders, pancreatic disease, hepatic disease, and reproductive abnormalities. [1a, 4] Over 1900 CFTR mutations have been identified to date and can be categorized into different classes based on the nature of the resulting CFTR defects. [4a, 5] The most-common mutation (c.1521-1523delCTT) encodes a mutant protein with a deletion of phenylalanine at position 508 (F508del-CFTR).…”