FFC#15/2018

Off-target effects of CFTR-modulators in preclinical infection models

FFC#15/2018

Off-target effects of CFTR-modulators in preclinical infection models

PRINCIPAL INVESTIGATOR

Cristina Cigana (Unità Infezioni e Fibrosi Cistica, divisione di Immunologia, Trapianti e Malattie Infettive, Istituto San Raffaele Milano)

RESEARCHERS

5

CATEGORY

AREA 3 Bronchopulmonary infection

DURATION

2 years

GOAL

€ 98.000 €

RESULTS

Through in-vitro experiments on a biobank of bacteria, the researchers evaluated whether the ivacaftor and lumacaftor modulators had an antibacterial activity, in addition to the action they have on CFTR. Researchers have shown that ivacaftor and lumacaftor have an antibacterial effect against S. aureus and also have a synergistic action with antibiotics and anti-Pseudomonas aeruginosa compounds. Tezacaftor, on the other hand, did not show antimicrobial activity and did not increase the efficacy of antibiotics. It is worth pointing out that ivacaftor and lumacaftor modify the virulence of P. aeruginosa which interferes with the CFTR functionality in the cells of the respiratory epithelium. The researchers also report that in experiments conducted on mice, infections are able to modulate the concentration of ivacaftor. These results can be used to improve the clinical procedure for administering modulators and antibiotics in CF patients chronically infected by P. aeruginosa e S. aureus.

OTHER RESULTS

FFC#1/2023

Tezacaftor, one of the components of Kaftrio, induces an accumulation of dihydroceramides both in vitro and in vivo in animal models

FFC#4/2023

Pseudopaline–aztreonam conjugates exhibited enhanced antimicrobial activity against Pseudomonas aeruginosa compared to aztreonam alone

FFC#10/2023

Several drugs already approved for human use inhibit the growth of P. aeruginosa, its virulence, or its ability to form biofilms in vitro