Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

The Netherlands
Induced pluripotent stem cells for identification of novel drug combinations targeting cystic fibrosis lung and liver disease

Project Coordinator

Hannover Medical School (MHH), REBIRTH - Cluster of Excellence, BREATH - German Center for Lung Research


Margarida Amaral University of Lisboa Lisboa, Portugal
Luis Galietta Istituto Giannina Gaslini Genova, Italy
Bob Scholte Erasmus MC Rotterdam Rotterdam, The Netherlands
Janet Rossant Hospital for Sick Children Toronto, Ontario, Canada
John Hanrahan McGill University Québec, Montreal, Québec (Canada)

Effective drugs for the treatment of Cystic Fibrosis (CF) patients with trafficking mutations are not yet available, and associated lung and liver pathologies remain untreatable with current interventions limited to organ transplantation. Novel compounds have to be identified, and in combination with known CFTR correctors, potentiators, and other small molecules, tailored to specific CFTR mutations, or even to the individual patient. Immortalized cell lines that overexpress mutant CFTR variants are typically used to screen candidate molecules but have proven to be poor predictors of clinical efficacy. The complexity of the mutant CFTR maturation and turnover kinetics requires the use of advanced cellular models that closely recapitulate the specific properties of the most clinically affected organs. To address these unmet needs we propose to generate a collection of primary bronchial epithelial cells and induced pluripotent stem cell (iPSC) lines from patients with common (F508del) and rare trafficking mutations, incl. known intragenic haplotypes with mild & severe phenotypes. The iPSC lines will be genetically corrected to generate adequate isogenic controls, and transgenic reporters will be introduced to facilitate high throughput (HT) screening. Compounds will be identified through HT screening followed by functional validation and identification of mechanism of action. Testing compound combinations in personalized surrogate models of CF lung and liver disease up to the pre-clinical stage will provide new treatment options for CF patients with different CFTR mutations.

E-Rare 2012 - Created by Toussaint Biger