Investigation of the sensitivity of CFTR variants to Ivacaftor/Lumacaftor in intestinal organoids model

Abstract

   Study of sensitivity of CFTR variants to targeted drugs allows to increase the number of patients with cystic fibrosis (CF) who can be prescribed effective therapy improving their quality and duration of life.

   Objective: to study the effect of the targeted drug Ivacaftor/Lumacaftor (I/L) on restoration of CFTR function on intestinal organoid (IO), derived from patients with different CFTR genotypes.

   Materials and methods: I/L effect was assessed using forskolin-induced swelling assay of IO.

   Results: IO cultures were obtained from 32 patients with 23 CFTR genotypes. I/L efficacy was assessed for 24 CFTR variants.

   Conclusion: for 11 CFTR gene variants, I/L targeted drug efficacy was demonstrated for the first time on the IO model.