INSTINCT - Induced pluripotent stem cells for identification of novel drug combinations targeting cystic fibrosis lung and liver disease
The INSTINCT project is currently supported under the frame of E-Rare-3, the ERA-Net for Research on Rare Diseases. INSTINCT receives a total funding of 1.2 Mio € for 36 months, starting from June 01, 2016. Each party is funded through the corresponding national funding agency that is a member of E-Rare-3, which for the German partner/ coordinator is the Federal Ministry of Education and Research (BMBF).
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Cystic fibrosis (CF) is a genetic disorder that affects mostly the lungs but also other organs inlcuding the pancreas, liver, and intestine, and is caused by numerous mutations in the so-called CFTR gene. Thus far, effective drugs for the treatment of most of the mutations are not available, and the search for new drugs is limited by the availability of airway cells carrying the respective mutations. INSTINCT is directly addressing this limitation by applying induced pluripotent stem cells (iPS cells). Novel genome engineering approaches are used and airway cells will be produced from these iPS cells to facilitate automated drug screening aiming at identifying new drugs for the treatment of CF, in particular for patients with class 2 mutations including the most common one, F508del. Moreover, our work will contribute to a better understanding of CF disease and to an improved treatment of CF.
Generation and use of CF-disease-specific iPS cells for drug screening and disease modeling. Blood from any patient can be reprogrammed into induced pluripotent stem (iPS) cells. These cells can be genetically modified, expanded and differentiated into the CFTR expressing airway and bile duct epithelia. These iPSC derivatives and patient-specific primary airway epithelia can be used a) to understand the molecular mechanisms underlying disease phenotypes, for example the molecular causes for different clinical phenotypes in CF patients with similar mutations, and b) in drug screening and discovery to determine the effects of candidate drugs and new compounds, and to identify target pathways.