Peter van Mourik

14 Chapter 1 Next, part 2 is focused on improving the implementation of intestinal organoids. Therefore, chapter 4 contains a protocol that has been implemented in four laboratories, and can be used worldwide to reduce inter-lab variability in both execution and results of the FIS assay, while chapter 5 examines the safety and success rate of rectal biopsy procedures for establishing intestinal organoid cultures. Part 3 explores the use of the FIS assay in intestinal organoids as a biomarker for clinical CFTR-modulator response by correlating FIS assay results with clinical trial data. Chapter 6 is an explorative study in patients homozygous for the F508del mutation, where we examine the correlations between clinical effects of lumacaftor/ ivacaftor treatment on several endpoints and intestinal organoid FIS when treated with lumacaftor/ivacaftor. In chapter 7 we assess whether intestinal organoid FIS response to curcumin, genistein, ivacaftor and lumacaftor/ivacaftor correlates with clinical response to these drugs in patients with a range of CFTR genotypes. Next, chapter 8 contains the study protocol of the HIT-CF Organoid Study, the first part of the HIT-CF Europe project. HIT-CF Europe aims to provide access to CFTR- modulators for patients with rare CFTR-mutations using organoids. Chapter 9 is a discussion of the results of the previous chapters and their combined implications for the use of intestinal organoids in the field of Cystic Fibrosis.