GM1 as Adjuvant of Innovative Therapies for Cystic Fibrosis Disease

Giulia Mancini, Nicoletta Loberto, Debora Olioso, Maria Cristina Dechecchi, Giulio Cabrini, Laura Mauri, Rosaria Bassi, Domitilla Schiumarini, Elena Chiricozzi, Giuseppe Lippi, Emanuela Pesce, Sandro Sonnino, Nicoletta Pedemonte, Anna Tamanini, Massimo Aureli

Research output: Contribution to journalArticlepeer-review


Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is expressed at the apical plasma membrane (PM) of different epithelial cells. The most common mutation responsible for the onset of cystic fibrosis (CF), F508del, inhibits the biosynthesis and transport of the protein at PM, and also presents gating and stability defects of the membrane anion channel upon its rescue by the use of correctors and potentiators. This prompted a multiple drug strategy for F508delCFTR aimed simultaneously at its rescue, functional potentiation and PM stabilization. Since ganglioside GM1 is involved in the functional stabilization of transmembrane proteins, we investigated its role as an adjuvant to increase the effectiveness of CFTR modulators. According to our results, we found that GM1 resides in the same PM microenvironment as CFTR. In CF cells, the expression of the mutated channel is accompanied by a decrease in the PM GM1 content. Interestingly, by the exogenous administration of GM1, it becomes a component of the PM, reducing the destabilizing effect of the potentiator VX-770 on rescued CFTR protein expression/function and improving its stabilization. This evidence could represent a starting point for developing innovative therapeutic strategies based on the co-administration of GM1, correctors and potentiators, with the aim of improving F508del CFTR function.

Original languageEnglish
JournalInt J Mol Sci
Issue number12
Publication statusPublished - Jun 24 2020


  • Adjuvants, Immunologic/chemistry
  • Aminophenols/chemistry
  • Aminopyridines/pharmacology
  • Benzodioxoles/pharmacology
  • Bronchi/drug effects
  • Chloride Channel Agonists/chemistry
  • Cystic Fibrosis/drug therapy
  • Cystic Fibrosis Transmembrane Conductance Regulator/genetics
  • Epithelial Cells/drug effects
  • G(M1) Ganglioside/chemistry
  • Humans
  • Mutation
  • Quinolones/chemistry
  • Therapies, Investigational


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