Distinctive lipid signatures of bronchial epithelial cells associated with cystic fibrosis drugs, including Trikafta.

JCI Insight
Nara LiessiAndrea Armirotti

Abstract

In recent years, a number of drugs have been approved for the treatment of cystic fibrosis (CF). Among them, newly released Trikafta, a combination of 3 drugs (VX-661/VX-445/VX-770), holds great promise to radically improve the quality of life for a large portion of patients with CF carrying 1 copy of F508del, the most frequent CF transmembrane conductance regulator (CFTR) mutation. Currently available disease-modifying CF drugs work by rescuing the function of the mutated CFTR anion channel. Recent research has shown that membrane lipids, and the cell lipidome in general, play a significant role in the mechanism of CFTR-defective trafficking and, on the other hand, its rescue. In this paper, by using untargeted lipidomics on CFBE41o- cells, we identified distinctive changes in the bronchial epithelial cell lipidome associated with treatment with Trikafta and other CF drugs. Particularly interesting was the reduction of levels of ceramide, a known molecular player in the induction of apoptosis, which appeared to be associated with a decrease in the susceptibility of cells to undergo apoptosis. This evidence could account for additional beneficial roles of the triple combination of drugs on CF phenotypes.

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Citations

Nov 4, 2020·Infection and Immunity·Katrin Anne BeckerErich Gulbins
Mar 7, 2021·International Journal of Molecular Sciences·Alessandra GhigoVirginia De Rose
Apr 4, 2021·International Journal of Molecular Sciences·Birgitta Strandvik
Apr 8, 2021·Expert Opinion on Drug Discovery·Miquéias Lopes-PachecoGuido Veit
Apr 12, 2021·The Journal of Biological Chemistry·Aaron Ions GardnerErich Gulbins
Jun 3, 2021·International Journal of Molecular Sciences·Valeria CapurroNicoletta Pedemonte
Nov 7, 2021·Cellular and Molecular Life Sciences : CMLS·Deanne H HryciwAndrew J McAinch

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Datasets Mentioned

BETA
MTBLS1480

Methods Mentioned

BETA
PCA

Software Mentioned

Markerlynx
Metabolights
Metaboanalyst
GraphPad Prism
Trikafta

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis