Exploring a new therapeutic target for Niemann-Pick C1 disease: the BET proteins

Our aim is to explore a new drug target for Niemann-Pick type C1 (NP-C1) disease, a rare genetic and ultimately fatal disease with no available curative therapy. We found that a specific pathway previously not studied in NP-C1 disease controls the production of NPC1 protein whose dysfunction causes the disorder. Our idea is that the inhibition of this pathway increases the amount of NPC1 variants that are still functional in cells and thereby prevent the disease progression. These variants occur in a large fraction of patients. Our preliminary results obtained both in patient-derived cells and in mutant mice are very encouraging, and we propose now to expand these experiments to solidify preclinical evidence for drug efficacy. The drugs that we aim to test here in patient-derived cells and in a mouse model of the disease are safe and already tested in clinical trials as anticancer drugs. The results obtained by this research project will help to validate a new strategy to alleviate the symptoms of this terrible disease using much wanted new drug targets.