FFC#23/2015

Targeting PI3Kγ scaffold function to activate airway CFTR, limit lung inflammation and promote bronchorelaxation in cystic fibrosis

FFC#23/2015

Targeting PI3Kγ scaffold function to activate airway CFTR, limit lung inflammation and promote bronchorelaxation in cystic fibrosis

PRINCIPAL INVESTIGATOR

Emilio Hirsch (Dipartimento di Biotecnologie Molecolari e Scienze Sanitarie, Centro di Biotecnologie Molecolari – Università di Torino)

Partner

Carlo Laudanna (Dip. di Patologia e Diagnostica, Divisione di Patologia Generale, Lab. di Traffico Cellulare e di Trasduzione Cellulare – Università di Verona)

RESEARCHERS

8

CATEGORY

AREA 4 Lung inflammation

DURATION

1 year

GOAL

€ 40.000 €

RESULTS

Researchers explored the ability of a peptide targeting the scaffold activity of PI3Kγ to function as a) bronchodilator, b) anti-inflammatory and c) CFTR potentiator. A mouse model of chronic lung inflammation (OVA sensitized mice) and human bronchial epithelial cells (F508del) were used. The peptide significantly elevates cAMP in the airways and limits methacholine-induced airways hyperresponsiveness in OVA mice. In the same model, the peptide reduces the neutrophilic lung inflammation. Finally, in F508del bronchial epithelial cells, it potentiates chloride currents per se and in combination with the gold standard potentiator VX770, upon pharmacological correction with VX809. Optimization of the peptide is ongoing and may pave the way to a peptide based aerosol therapy to be used in combination with standard-of-care CFTR correctors/potentiators.

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