Although highly effective CFTR modulator therapy (HEMT) is providing major benefits to people with cystic fibrosis (CF), the inflammatory processes progressively damaging pulmonary tissues are not halted. Thus, there is an urgent need for anti-inflammatory agents complementary to HEMT to be given by the pulmonary route to people with CF.
The synthetic molecule GY971, developed in previous FFC#22/2019 and FFC#10/2022 projects,  shows anti-inflammatory action in bronchial epithelial cells in vitro and murine lungs in vivo. The hypothesis is that GY971 could be further developed to obtain an innovative anti-inflammatory drug tailored to the needs of people with CF. The aim of this project is to consolidate and extend the evidence of its anti-inflammatory efficacy and collect preliminary safety data.
GY971 will be tested in cells in vitro, bronchial and nasal epithelial cells obtained ex vivo, in murine lungs and zebrafish animal models in vivo. Preliminary safety tests will be performed in advanced in silico, in vitro and in vivo models to exclude undesired effects. The analysis will be conducted in collaboration with FFC Ricerca CFaCore and Servizio Colture Primarie.
GY971 appears promising for the future development of combinatorial anti-inflammatory treatments together with HEMT. The tests of efficacy and safety, extended and consolidated in this project in further models ex vivo, in vivo and in vitro, could stimulate the  design of pharmaceutical formulations of GY971 for pulmonary delivery and enhance the chances for a safe and effective innovative anti-inflammatory compound for people with CF.