People with cystic fibrosis (pwCF) are prone to contracting bacterial lung infections with Pseudomonas aeruginosa, which have been linked to chronic inflammation and oxidative stress in the lungs.
Although Trikafta/Kaftrio has been shown to improve the quality of life in pwCF, clinical trials have shown variable responses to this drug formulation. This variability could be due to lung inflammation and oxidative status induced by recurrent P. aeruginosa infection.
Anti-inflammatory/antioxidant therapies are therefore of particular interest in pwCF to slow down the progression of lung damage and, hopefully, to improve the Kaftrio efficacy and their quality of life.
The aim of the project will be to explore the effect of anti-inflammatory/antioxidants on the recovery of CFTR activity induced by Kaftrio in nasal epithelial cells.
The main idea is that anti-inflammatory/antioxidant drugs, by reducing tissue damage caused by chronic inflammation and oxidative stress, may increase the efficacy of CFTR modulators.
Furthermore, in order to reduce inflammation-mediated lung tissue damage without blunting the immune response, that is crucial to defend against infections, bacterial proliferation in murine models will be checked in parallel.
Anti-inflammatory/antioxidant agents are already approved therapy for autoimmune and inflammatory diseases. Therefore, testing and confirming the anti-inflammatory and antioxidant activities of those compounds in CF patient-derived tissues could be important to develop personalized treatments combined with CFTR modulators.