A minimal unified model of disease trajectories captures hallmarks of multiple sclerosis

Handle URI:
http://hdl.handle.net/10754/623066
Title:
A minimal unified model of disease trajectories captures hallmarks of multiple sclerosis
Authors:
Kannan, Venkateshan; Kiani, Narsis A.; Piehl, Fredrik; Tegner, Jesper ( 0000-0002-9568-5588 )
Abstract:
Multiple 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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Citation:
Kannan 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.
Publisher:
Elsevier BV
Journal:
Mathematical Biosciences
Issue Date:
29-Mar-2017
DOI:
10.1016/j.mbs.2017.03.006
Type:
Article
ISSN:
0025-5564
Sponsors:
We 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.
Additional Links:
http://www.sciencedirect.com/science/article/pii/S0025556416302358
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division; Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorKannan, Venkateshanen
dc.contributor.authorKiani, Narsis A.en
dc.contributor.authorPiehl, Fredriken
dc.contributor.authorTegner, Jesperen
dc.date.accessioned2017-04-10T07:49:48Z-
dc.date.available2017-04-10T07:49:48Z-
dc.date.issued2017-03-29en
dc.identifier.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.en
dc.identifier.issn0025-5564en
dc.identifier.doi10.1016/j.mbs.2017.03.006en
dc.identifier.urihttp://hdl.handle.net/10754/623066-
dc.description.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.en
dc.description.sponsorshipWe 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.en
dc.publisherElsevier BVen
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0025556416302358en
dc.rightsUnder a Creative Commons license, http://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.titleA minimal unified model of disease trajectories captures hallmarks of multiple sclerosisen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputer, Electrical and Mathematical Sciences and Engineering (CEMSE) Divisionen
dc.identifier.journalMathematical Biosciencesen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionUnit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Solna, Karolinska Institutet 17176, Sweden.en
dc.contributor.institutionUnit of Computational Medicine, Center for Molecular Medicine, Department of Medicine, Solna, Karolinska Institutet 17176, Swedenen
dc.contributor.institutionUnit of NeuroImmunology, Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska University Hospital L8 17176, Stockholm, Sweden.en
kaust.authorTegner, Jesperen
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