FFC#4/2016

Development of a PI3Kγ-derived peptide as a novel F508del-CFTR potentiator

FFC#4/2016

Development of a PI3Kγ-derived peptide as a novel F508del-CFTR potentiator

PRINCIPAL INVESTIGATOR

Alessandra Ghigo (Dipartimento di Biotecnologia Molecolare e Scienze della Salute, Università di Torino)

RESEARCHERS

7

CATEGORY

AREA 1 Therapies to correct the underlying defect

DURATION

1 year

GOAL

€ 50.000 €

RESULTS

The peptide potentiated F508del-CFTR and was significantly more efficient than the gold-standard CFTR potentiator VX-770 both in bronchial monolayers and in intestinal organoids from F508del patients. Furthermore, the peptide improved F508del-CFTR conductance even after chronic Orkambi®, without interfering with channel stability. On the contrary, the peptide per se ameliorated F508del-CFTR stability at the plasma membrane. The PI3Kγ-derived peptide is covered by patent number TO2014A00110 – WO/2016/103176 and received the Orphan Drug Designation by the European Medicinal Agency (EU/3/17/1859) in 2017. Researchers intend to develop the PI3Kγ peptide as a novel medicinal product that could be used, either alone or in combination with gold-standard therapies, in F508del patients. With the Extension project FFC#11/2017 they intend to complete the chemical optimization and the characterization of the therapeutic potential of PI3Kγ peptides (parent and optimized) in CF relevant models.

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