Cystic fibrosis is a rare genetic disease caused by several mutations in the CFTR gene, which codes for a membrane protein with a chlorine channel function, called the cystic fibrosis transmembrane conductance regulator, or CFTR protein.

A new all-Italian study, published in the journal Cellular and Molecular Life Sciences, has revealed a possible alternative therapy for cystic fibrosis involving two drugs already in clinical use for other diseases, a protein inhibitor (camostat), a coenzyme (S-adenosyl methionine) and a food substance, turmeric extract. These substances can induce biochemical and epigenetic changes - heritable changes in gene expression that do not alter the DNA sequence - in the epithelial sodium channel (ENaC), which interacts with the CFTR protein in determining the pathophysiology of cystic fibrosis.

The research, a collaboration between Sapienza University of Rome, the University of Foggia and the University of Bari, was coordinated by Marco Lucarelli of the Department of Experimental Medicine and Fiorentina Ascenzioni of Charles Darwin Department of Biology and Biotechnology of Sapienza, and Massimo Conese of the University of Foggia.

'Although precision therapy for cystic fibrosis acting on the CFTR protein is now possible (even if only for certain mutations), the proposed therapeutic approach, which instead acts on the ENaC channel, could be performed,' says Marco Lucarelli, 'at the same time as precision therapy in order to enhance its effect, or as an alternative to it in cases where the main CFTR defect cannot be effectively acted upon.

Moreover, the therapeutic substances proposed in this study - two drugs already in clinical use for other diseases and a food substance - are more likely to be used in the clinic than experimental substances with safety studies not yet carried out.

'Understanding the epigenetic mechanisms involved in cystic fibrosis,’ concludes Marco Lucarelli, 'opens the way to new possibilities for treating this disease, in which epigenetics itself could be considered a therapeutic target.

References

Downregulation of epithelial sodium channel (ENaC) activity in cystic fibrosis cells by epigenetic targeting – Giovanna Blaconà, Roberto Raso, Stefano Castellani, Silvia Pierandrei, Paola Del Porto, Giampiero Ferraguti, Fiorentina Ascenzioni, Massimo Conese, Marco Lucarelli – Cellular and Molecular Life Sciences (2022) https://doi.org/10.1007/s00018-022-04190-9

Further Information

Marco Lucarelli
Department of Experimental Medicine
marco.lucarelli@uniroma1.it