FFC#18/2016

Interfering with glycosaminoglycans during Pseudomonas aeruginosa chronic lung infection: pre-clinical exploitation of a novel therapeutic strategy for cystic fibrosis

FFC#18/2016

Interfering with glycosaminoglycans during Pseudomonas aeruginosa chronic lung infection: pre-clinical exploitation of a novel therapeutic strategy for cystic fibrosis

PRINCIPAL INVESTIGATOR

Cristina Cigana (Unità Infezioni e Fibrosi Cistica, Divisione Immunologia, Trapianto e Malattie infettive, Istituto Scientifico San Raffaele, Milano)

Partner

Annamaria Naggi (Istituto Ricerche Cliniche e Biochimiche G. Ronzoni, Milano)

RESEARCHERS

8

CATEGORY

AREA 4 Lung inflammation

DURATION

1 year

GOAL

€ 60.000 €

RESULTS

Efficacy studies demonstrated that PS (sulphatated polysaccharides) named C3 and C23 significantly competed with glycosaminoglycans (GAG) and inhibited markers of inflammation induced by acute and chronic lung infection in murine models infected by Pseudomonas aeruginosa. In addition, they significantly reduced P. aeruginosa burden during chronic lung infection. C3 and C23 were administrated to mice by subcutaneous way and their pharmacokinetic characteristics were studied. Analysis in human respiratory samples showed that GAG, including Heparin Sulphate (HS), are present in the airways of CF patients and they correlate with markers of inflammation and tissue damage. These data support the further evaluation of C3 and C23 as novel therapeutic molecules to counteract excessive inflammation induced by P. aeruginosa pulmonary infections in CF patients.

OTHER RESULTS

FFC #3/2024

Two molecules are effective in activating Heat Shock Proteins and enhancing the action of CFTR correctors with the F508del mutation in vitro.

FFC#5/2024

Some peptide nucleic acids (PNAs) re-sensitise Pseudomonas aeruginosa to the antibiotic meropenem in vitro and reduce its virulence.

FFC#1/2023

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