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    Rights statement: 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.

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Determining disease interventions strategies using spatially resolved simulations

Research output: Contribution to Journal/MagazineJournal articlepeer-review

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  • Mark Read
  • Paul Andrews
  • Jon Timmis
  • Richard Williams
  • Richard Greaves
  • Huiming Sheng
  • Mark Coles
  • Vipin Kumar
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Article numbere80506
<mark>Journal publication date</mark>14/11/2013
<mark>Journal</mark>PLoS ONE
Issue number11
Volume8
Number of pages14
Publication StatusPublished
<mark>Original language</mark>English

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.

Bibliographic note

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.