ABCMdb

PMID: 25003014

Dekkers JF, van der Ent CK, Beekman JM
Novel opportunities for CFTR-targeting drug development using organoids.
Rare Dis. 2013 Nov 11;1:e27112. doi: 10.4161/rdis.27112. eCollection 2013., [PubMed]

Sentences

No. Mutations Sentence Comment

15 ABCC7 p.Gly551Asp Rare Diseases 2013; 1:e27112 Addendum to: Dekkers JF, Wiegerinck CL, de Jonge HR, Bronsveld I, Janssens HM, de Winter-de Groot KM, Brandsma AM, de Jong NW, Bijvelds MJ, Scholte BJ, et al. A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat Med 2013; 19:939-45; PMID:23727931; http:// dx.doi.org/10.1038/nm.3201 established drugs.5 Thus far, the CFTR potentiator Kalydeco (VX-770) is the only CFTR-targeting drug commercially available and it is approved for a select subset of CF subjects (< 4%) expressing the gating mutant CFTR-G551D.6,7 This exciting development demonstrates that CFTR-directed pharmacotherapy is feasible, and may possibly be designed for the majority of subjects with CF. Login to comment 41 ABCC7 p.Ala455Glu FIS varied greatly between organoids derived from different CF subjects, and was largest in organoids from patients with milder CF that express CFTR-A455E.17,24 We detected FIS in all organoids expressing CFTR-F508del, also when it was expressed from just a single allele. Login to comment 72 ABCC7 p.Gly551Asp This model was successfully applied to register Kalydeco for CFTR-G551D-expressing subjects, and currently novel genotypes are being selected for Kalydeco treatment.28 Especially for subjects expressing complex or rare CFTR genotypes, in vitro replication of CFTR mutations in ectopic expression models can be difficult (e.g., for splice site mutations). Login to comment 110 ABCC7 p.Gly551Asp A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. Login to comment