Peter van Mourik

183 General discussion 35 . Elexacaftor has been the first clinically approved next-generation corrector, and triple combination of tezacaftor/elexacaftor/ivacaftor treatment results in astonishing improvements for patients with at least one F508del allele, although large treatment effect variability can be observed 36,37 . A major issue with current CFTR-modulators are their extremely high prices that significantly limit access to these drugs for patients with CF, especially (but not solely) in less economically developed areas such as Eastern Europe. Even in the Netherlands and United Kingdom it has taken several years for lumacaftor/ivacaftor to be reimbursed 38,39 . Figure 1: Different CFTR-targeting drugs can be researched using intestinal organoids. Intestinal organ- oids as a model can be very helpful to study the efficacy of potential gene therapy vectors, enable robust CFTR-function measurements and due to their high proliferation rate can be applied for high-content drug screening. Moreover, CFTR-modulating drugs that act on different cellular mechanisms can be studied. 9