Violeta Balbas-Martinez 1 2, Leire Ruiz-Cerdá 1 2, Itziar Irurzun-Arana 1 2, Ignacio González-García 1, An Vermeulen 3 4, José David Gómez-Mantilla 1, Iñaki F Trocóniz 1 2 , PLoS One. 2018 Mar 7;13(3):e0192949. doi
A systems pharmacology model for inflammatory bowel disease
In this article, we propose a logic model for Inflammatory Bowel Disease (IBD) which consists of 43 nodes and 298 qualitative interactions. The model presented is able to describe the pathogenic mechanisms of the disorder and qualitatively describes the characteristic chronic inflammation. A perturbation analysis performed on the IBD network indicates that the model is robust. Also, as described in clinical trials, a simulation of anti-TNFα, anti-IL2 and Granulocyte and Monocyte Apheresis showed a decrease in the Metalloproteinases node (MMPs), which means a decrease in tissue damage. In contrast, as clinical trials have demonstrated, a simulation of anti-IL17 and anti-IFNγ or IL10 overexpression therapy did not show any major change in MMPs expression, as corresponds to a failed therapy. The model proved to be a promising in silico tool for the evaluation of potential therapeutic targets, the identification of new IBD biomarkers, the integration of IBD polymorphisms to anticipate responders and non-responders and can be reduced and transformed in quantitative model/s.
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