IDENTIFICATION OF NOVEL COMPOUNDS FOR THE PHARMACOLOGICAL CORRECTION OF CYSTIC FIBROSIS CHLORIDE TRANSPORT DEFECT

Cystic fibrosis (CF) is one of the most frequent genetic diseases, characterized by a progressive and irreversible damage to the lungs and the pancreas. CF is caused by mutations that abolish the function of a protein expressed in the epithelial cells of many organs. The affected protein, called CFTR, is needed to transport chloride. So far, there are no effective therapies able to cure the CF basic defect and to stop the progression of the disease. Nevertheless, there are evidences obtained on cultured cells that the function of the mutant CFTR may be restored using proper drugs. To discover such drugs, we have chosen a strategy based on the screening of large collection of chemical compounds using an automated assay and cultured cells. The most active compounds arising from the screening will be evaluated in more detail with other techniques. Using this approach, we have identified in the last years a series of compounds with high efficacy and promising characteristics. The present project aims at continuing our work with two main goals: 1) to improve the potency and effectiveness of compounds identified so far; 2) to identify other active compounds in order to increase the probability of finding substances suitable as drugs for CF therapy.