Project Leader: Dr. Oscar Moran
H2020 Research and Innovation Action
Cystic fibrosis is a lethal hereditary disease where mutations in the gene cftr produce a defect on salt transport in epithelial cells, with serious consequences in several organs, like lungs, pancreas and intestine. The aim of the project is to develop small molecules, named anionophores, able to recover the chloride and bicarbonate transport in cells of cystic fibrosis patients. The novelty of this approach is the possibility to correct the salt transport defect pharmacologically, independently of the mutation that causes the CFTR malfunction. The project covers all aspects of drug discovery, from chemical synthesis to preclinical studies in animal models.
IBF’s main tasks fall under the Cell Physiology and Biophysics Work Package, whose aim is to provide a functional characterisation of selected compounds synthesised by the chemistry group at Burgos, and identified by the drug screening group at the G. Gaslini Hospital in Genova. This data, together with medical chemistry analysis by Avidin, Hungary, will be successively optimised by the chemistry group. Successive development of drug candidates will comprise formulation of administration strategies, organoid and animal model studies and design of industrial production of substances, with the participation of small industry and academia groups in Germany, Spain and Denmark.
The IBF group will provide the parameters to objectively evaluate the anionophores, and will measure the impact of the anion transport induced by the compounds on the physiological behaviour of relevant cellular preparations in vitro. The specific objectives are:
- Biophysical, biochemical and physiological characterization of the anionophores transport properties in model and cellular preparations.
- Assessment of the physiological impact of the anionophore-induced anion transport on normal and cystic fibrosis bronchial cell models