Persons with cystic fibrosis (CF) have numerous defects in the metabolism of a specific class of lipids, called sphingolipids, and one of the enzymes involved in this metabolism, sphingosine-1-phosphate lyase (SPL), is an interesting drug target. In fact, blocking its activity improves lung inflammation in a mouse model of CF and, at the same time, it has a powerful antimicrobial activity. The goal of the project, extension of the FFC#16/2020 pilot is to inhibit SPL both in the host and in the pathogen, such as Aspergillus fumigatus, thus obtaining two opposite effects, but both advantageous. The research group aims to identify potential inhibitors of host and Aspergillus SPL, which will be tested on purified proteins and in vitro and in vivo models. The most promising inhibitors will then be prepared in such a way as to allow direct administration into the lungs, in order to limit the side effects.

XIX Convention FFC Ricerca – download here a brief presentation of the project