Personalizing CFTR modulator therapies

Abstract

over 2000 genetic mutations that can cause CF, resulting in many phenotypes. Recently new drugs were developed that treat the disease at the origin of the problem; they enhance the function of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein which is not functioning properly in CF. These potentially life saving drugs are currently only available for part of the CF population and especially patients with a rare mutation often don’t qualify for a treatment. By culturing stem cells of a patient in the lab, we can generate organoid which can be seen as a sort of mini-organs. This culture technique generates many options for research and individualised drug testing without the need to test a treatment in a patient.

Research in this thesis shows how intestinal organoids can be used to treat patients with CF. It shows for example how organoids can be used to identify effective treatments for (groups of) patients. Because of this research a number of CF patients with a rare CFTR mutation was already successfully selected for a life changing treatment. This thesis also provides the basis for a current European study in which treatments are selected for about 2000 European CF patients with a rare CFTR mutation. It is expected that in the near future the organoid model can not only be used for research in patients with CF but also for patients with other diseases.