FFC#20/2019

Evaluation of anti-inflammatory treatments for CF lung disease in murine models of lung infection in vivo: insights on the anti-inflammatory effect of β-sitosterol and anti-inflammatory/anti-infective activity of L-miglustat

FFC#20/2019

Evaluation of anti-inflammatory treatments for CF lung disease in murine models of lung infection in vivo: insights on the anti-inflammatory effect of β-sitosterol and anti-inflammatory/anti-infective activity of L-miglustat

PRINCIPAL INVESTIGATOR

Maria Cristina Dechecchi (Azienda Ospedaliera Universitaria Integrata di Verona, Laboratorio di Patologia Molecolare-Laboratorio Analisi)

Partner

Annalisa Guaragna (Università di Napoli Federico II, Dip. di Scienze Chimiche)

RESEARCHERS

11

CATEGORY

AREA 4 Lung inflammation

DURATION

1 year

GOAL

€ 65.000 €

RESULTS

The research team exploited a mouse model of chronic lung infection with Pseudomonas aeruginosa to evaluate the anti-inflammatory effects of beta-sitosterol (BSS) and L-miglustat. The test was also conducted with the collaboration with the CFaCore service.
The results of this project, a continuation of the previous FFC#23/2018), allowed to evaluate the effectiveness in reducing lung inflammation and the ability to fight infection of the two compounds. BSS and L-miglustat would facilitate immune response mechanisms by showing anti-inflammatory and anti-infective properties. The experiments highlighted a decrease in the amount of bacteria detected in the airways in mice with chronic P. aeruginosa infection after treatment with BSS and L-miglustat. This preclinical study provides a proof of concept on the properties of BSS and L-miglustat that could achieve the orphan drug designation (ODD) for the treatment of chronic P. aeruginosa infections.

Pubblicaions

  • De Gregorio E, Esposito A, Vollario A et al. N-Nonyloxypentyl-l-Deoxynojirimycin Inhibits Growth, Biofilm Formation and Virulence Factors Expression of Staphylococcus aureus, Antibiotics, 2020 Jun 26;9(6):362
  • De Fenza M, D’Alonzo D, Esposito A et al. Exploring the effect of chirality on the therapeutic potential of Nalkyl-deoxyiminosugars: anti-inflammatory response to Pseudomonas aeruginosa infections for application in CF lung disease, Eur J Med Chem, 2019 Aug 1;175:63-71
  • Esposito A, D’Alonzo D, De Fenza M et al. Synthesis and Therapeutic Applications of Iminosugars in Cystic Fibrosis, International Journal of Molecular Sciences 2020 May; 21(9): 3353

Congress abstracts

  • Esposito A, De Fenza M, D’Alonzo M et al. N-Alkylated L-iminosugars as novel anti-inflammatory and anti-biofilm tools for cystic fibrosis lung infections, 7th EFMC International Symposium on Advances in Synthetic and Medicinal Chemistry, Athene, Greece, 1-5 Settembre 2019
  • Esposito A, De Fenza M, D’Alonzo D et al. N-Alkylated L-Iminosugars as novel anti-inflammatory and anti-biofilm tools for Cystic Fibrosis Lung Infections, 6th EFMC Young Medicinal Chemist Symposium, Athene, Grecia, 5-6 Settembre 2019

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