Abstract | BACKGROUND: The most recent modulator combination, elexacaftor/ tezacaftor/ivacaftor (Trikafta®), has been shown to improve clinical outcomes in most patients with cystic fibrosis (PwCF). Unfortunately, the clinical benefits are sometimes variable; thus, improving our knowledge of the possible causes of this variability can help reduce it. METHODS: Circulating mononuclear cells (CMCs) and plasma were collected from 16 PwCF (including those on Trikafta® therapy) and 4 non-CF subjects. Cystic fibrosis transmembrane conductance regulator (CFTR) activity and matrix metalloprotease 9 (MMP9) expression were monitored before and after therapy, together with some clinical parameters. The relationship between MMP9 expression and the modulation of the extracellular-regulated 1/2 (ERK1/2) and nuclear factor-kB ( NF-kB) pathways was also analyzed. RESULTS: MMP9, markedly expressed in the CMCs and plasma of all the patients included in the study, was downregulated in the clinically responsive PwCF. In the non-responder, the MMP9 levels remained high. The modulation of MMP9 following treatment with Trikafta® may be controlled by the NF-kB pathway. CONCLUSIONS: These data strongly suggest that MMP9 downregulation is a potential biomarker of therapy efficacy and that it could be useful in understanding the molecular events underlying the variable clinical responses of patients to Trikafta®. This knowledge could be helpful for future studies of personalized medicine and thereby ensure improvements in individual responses to therapies.
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Authors | Michela Capraro, Marco Pedrazzi, Roberta De Tullio, Marcello Manfredi, Federico Cresta, Carlo Castellani, Monica Averna |
Journal | International journal of molecular sciences
(Int J Mol Sci)
Vol. 24
Issue 17
(Aug 29 2023)
ISSN: 1422-0067 [Electronic] Switzerland |
PMID | 37686190
(Publication Type: Journal Article)
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Chemical References |
- Cystic Fibrosis Transmembrane Conductance Regulator
- Matrix Metalloproteinase 9
- NF-kappa B
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Topics |
- Humans
- Cystic Fibrosis Transmembrane Conductance Regulator
(genetics)
- Cystic Fibrosis
(drug therapy, genetics)
- Matrix Metalloproteinase 9
(genetics)
- NF-kappa B
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