Determining disease interventions strategies using spatially resolved simulations

Read, Mark and Andrews, Paul and Timmis, Jon and Williams, Richard and Greaves, Richard and Sheng, Huiming and Coles, Mark and Kumar, Vipin (2013) Determining disease interventions strategies using spatially resolved simulations. PLoS ONE, 8 (11). ISSN 1932-6203

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Abstract

Predicting efficacy and optimal drug delivery strategies for small molecule and biological therapeutics is challenging due to the complex interactions between diverse cell types in different tissues that determine disease outcome. Here we present a new methodology to simulate inflammatory disease manifestation and test potential intervention strategies in silico using agent-based computational models. Simulations created using this methodology have explicit spatial and temporal representations, and capture the heterogeneous and stochastic cellular behaviours that lead to emergence of pathology or disease resolution. To demonstrate this methodology we have simulated the prototypic murine T cell-mediated autoimmune disease experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. In the simulation immune cell dynamics, neuronal damage and tissue specific pathology emerge, closely resembling behaviour found in the murine model. Using the calibrated simulation we have analysed how changes in the timing and efficacy of T cell receptor signalling inhibition leads to either disease exacerbation or resolution. The technology described is a powerful new method to understand cellular behaviours in complex inflammatory disease, permits rational design of drug interventional strategies and has provided new insights into the role of TCR signalling in autoimmune disease progression.

Item Type:
Journal Article
Journal or Publication Title:
PLoS ONE
Additional Information:
Copyright: © 2013 Read et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700
Subjects:
ID Code:
67558
Deposited By:
Deposited On:
15 Nov 2013 09:46
Refereed?:
Yes
Published?:
Published
Last Modified:
23 Oct 2020 02:19