FFC#22/2018

Preclinical testing in cystic fibrosis of a repurposed molecule targeting HMGB1

FFC#22/2018

Preclinical testing in cystic fibrosis of a repurposed molecule targeting HMGB1

PRINCIPAL INVESTIGATOR

Marco Emilio Bianchi (Divisione Genetica e Biologia Cellulare, Unità dinamica della cromatina, Ospedale San Raffaele, Milano)

RESEARCHERS

3

CATEGORY

AREA 4 Lung inflammation

DURATION

1 year

GOAL

€ 65.000 €

RESULTS

Researchers found that PAM (Pamoic Acid) is a compound neutralizing the HMGB1 protein, an important pro-inflammatory agent. So they wanted to test PAM in murine models (C57 mice) infected with Pseudomonas aeruginosa, with the aim to investigate if it might reduce lung infection and inflammation. Specifically, they carried out experiments to investigate both toxicity and efficacy of PAM. They have shown PAM does not have acute toxicity when delivered by aerosol at concentrations ≤3 Mm; it has significant efficacy in reducing inflammatory cells in the bronchoalveolar lavage in an acute mouse model of Pseudomonas infection; moreover, it may be effective in a chronic model even in a lower concentration range. PAM cannot cross lipid membranes so that it is not suitable to be systemically absorbed. However, researchers cannot exclude that formulations that allow systemic diffusion might be more effective than aerosol. The results obtained in Pseudomonas infected mice models suggest PAM is candidate to represent an effective drug against inflammation in CF lung disease.

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