The potentiator Ivacaftor (Kalydeco), also included in the triple combination Kaftrio or Trikafta, might display, as a side effect, the reduction in the amount of CFTR protein at the apical cell membrane. A similar reducing effect may also be caused by Pseudomonas aeruginosa infection. Such a negative effect can be compensated by two lipid compounds, namely GM1 ganglioside and cholesterol (or its analogue beta-sitosterol); they are already on the market to treat other pathologies. The proposal intends to investigate if the exogenous administration of those lipids, which are deficient in the CF bronchial epithelial cells, can increase the efficiency of correctors and potentiators and the functional recovery of CFTR-F508del, even when P. aeruginosa infections are present, with a stabilizing effect. Researchers will work in primary cells from explanted CF lungs. The approach could represent the starting point for the development of new therapeutic strategies based on the association of lipids and modulators, to improve the effectiveness of CFTR modulators themselves.
WHO ADOPTED THE PROJECT
€ 20.000
€ 20.000
Delegazione FFC di Vigevano
€ 47.000