Ex-vivo experiments on leukocytes were conducted to evaluate the modification of the proteome in response to the treatment with VX-770. In this project, leukocytes were isolated from peripheral blood of CF patients carrying different mutations (class III and IV with gating and non-gating defect with residual CFTR function).
The cells were then treated with VX-770 (ivacaftor) and subsequently, their proteome has been analysed using laboratory techniques such as high-resolution mass spectrometry nano-LC chromatography and GST-HS-YFP assay. In addition, the researchers used bioinformatics tools to evaluate the interactions among proteins and identify possible altered pathways. The researchers isolated 1545 proteins and investigated those proteins of the cells in which the activity of CFTR was restored after VX-770 treatment. The data obtained allowed the identification of two pathways, involved in the leukocyte transendothelial migration and maintenance of cellular structure, which were found to be altered in the cells that responded to treatment with VX-770. Further studies could lead to the identification of biomarkers useful for the evaluation or prediction of the efficacy of new therapies.

Congress abstracts

• Franchi A, Pedrazzi M, De Tullio R et al. Identification of new leukocytes biomarkers directly related to a restored CFTR activity by shotgun proteomic analysis, 43rd European Cystic Fibrosis Conference, 2020 (virtual conference)