A minimal unified model of disease trajectories captures hallmarks of multiple sclerosis
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Online Publication Date2017-03-29
Print Publication Date2017-07
Permanent link to this recordhttp://hdl.handle.net/10754/623066
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AbstractMultiple Sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) causing demyelination and neurodegeneration leading to accumulation of neurological disability. Here we present a minimal, computational model involving the immune system and CNS that generates the principal subtypes of the disease observed in patients. The model captures several key features of MS, especially those that distinguish the chronic progressive phase from that of the relapse-remitting. In addition, a rare subtype of the disease, progressive relapsing MS naturally emerges from the model. The model posits the existence of two key thresholds, one in the immune system and the other in the CNS, that separate dynamically distinct behavior of the model. Exploring the two-dimensional space of these thresholds, we obtain multiple phases of disease evolution and these shows greater variation than the clinical classification of MS, thus capturing the heterogeneity that is manifested in patients.
CitationKannan V, Kiani NA, Piehl F, Tegner J (2017) A minimal unified model of disease trajectories captures hallmarks of multiple sclerosis. Mathematical Biosciences. Available: http://dx.doi.org/10.1016/j.mbs.2017.03.006.
SponsorsWe thank Drs. Maja Jagodic, Ingrid Kockum, Tomas Olsson, David Gomez-Cabrero, and Gilad Silberberg for critical discussions and comments. This work was supported by the following grants to J.T; Hjrnfonden, ALF, STATegra (FP7), Torsten Sderberg Foundation, Stockholm County Council, Swedish excellence center for e-science and Swedish Research Council (3R program MH and project grant NT). N.K was supported by a fellowship from VINNOVA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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