Pharmacological modulation of ion transport to treat the basic defect in cystic fibrosis

Cystic fibrosis (CF) is caused by mutations that impair the function of CFTR, a protein localized on the membrane of epithelial cells. Loss of CFTR function has consequences in multiple organs. However, the lung disease is a major cause of morbidity and mortality in CF. The lack of CFTR impairs the innate natural defences of the airways causing bacterial infection and mucus accumulation. In many patients, the progressive loss of respiratory function in the last stage of the disease results into lung transplant as a life-saving intervention. The basic defect in CF can be targeted with pharmacological strategies. Depending on the type of mutations, CFTR activity can be restored with specific drugs called correctors and potentiators. My research group has been particularly active in the search of effective correctors and potentiators to treat the basic defect in CF. Moreover, the basic defect in CF can be corrected by targeting other proteins. We identified a protein that could circumvent defective CFT, a strategy that could be important for those CF patients carrying mutation that are not sensitive to correctors and potentiators. We are now working on to confirm its importance as a therapeutic target in CF and to find pharmacological activators. The "Total Award" amount indicated for this project represents the share of the funding of the Telethon Foundation for research by the Tigem institute from July 2016 until last budget year, calculated based on the size of the research group.