FFC#29/2014

Properties of airway mucus in cystic fibrosis: their modification by changes in the activity of CFTR and after application of bicarbonate

FFC#29/2014

Properties of airway mucus in cystic fibrosis: their modification by changes in the activity of CFTR and after application of bicarbonate

PRINCIPAL INVESTIGATOR

Olga Luisa A. Zegarra (U.O.C. Genetica Medica, Istituto “Giannina Gaslini”, Genova)

RESEARCHERS

12

CATEGORY

AREA 5 Clinical and Epidemiological research

DURATION

1 year

GOAL

€ 38.000

RESULTS

Researchers determined that in CF mucus nanobeads have lower diffusion coefficient, and the elastic and viscous moduli are higher than in non-CF mucus. Also, they found that 25% correction of F508del mutation with lumacaftor is enough to improve significantly CF mucus properties. Surprisingly, also incubation with amiloride, a compound that reduces fluid absorption but not the secretion of bicarbonate, improved CF mucus properties. Regarding inhalation of bicarbonate by CF patients, a pilot clinical trial is planned. In conclusion, CF mucus properties can be recovered in vitro either improving the hydration of the airways or increasing the activity of the mutated protein with a corrector compound, probably by increasing bicarbonate secretion. The results of the clinical trial will permit to determine whether bicarbonate, a low cost and mutation-independent treatment, can improve the properties of CF sputums.

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