Using CF bronchial epithelial cells as an experimental model, the researchers reported that there is a reduced amount of GM1 ganglioside within the plasma membrane (PM). Furthermore, using radioactive probes, they have shown that GM1 and CFTR reside in the same PM compartment. Interestingly, the researchers have also reported that the low efficacy of Orkambi, lumacaftor corrector (VX809) and ivacaftor potentiator (VX770) in the lungs is probably due to the instability of the membrane in CFTR mutated cells. In fact, it has been reported that VX770 modifies the lipid content of the plasma membrane and reduces the effect of the VX809 corrector. The results also show how the administration of GM1 reduces the negative effects of VX770 and those caused by Pseudomonas aeruginosa infection. GM1 gangliosides, already in use for the treatment of other pathologies such as neurological diseases, including ischemic brain lesions, stabilize the plasma membrane and could be used as an adjuvant to modulators already available for the treatment of cystic fibrosis.

Pubblications

• Mancini G, Loberto N, Olioso D et al. GM1 as Adjuvant of Innovative Therapies for Cystic Fibrosis Disease, International Journal of Molecular Sciences 2020 Jun 24;21(12):4486
• Loberto N, Mancini G, Bassi R et al. Sphingolipids and plasma membrane hydrolases in human primary bronchial cells during differentiation and their altered patterns in cystic fibrosis, Glycoconjugate Journal 2020 Jul 14.