Therapeutic targeting of oligodendrocytes in an agent-based model of multiple sclerosis
Georgia R. Weatherley, Robyn P. Araujo, Samantha J. Dando, Adrianne L. Jenner
TL;DR
This paper introduces a new computational model to study how targeting oligodendrocytes could help treat multiple sclerosis by promoting tissue repair and stabilizing lesions.
Contribution
The paper presents a novel, open-source agent-based model to explore therapeutic strategies targeting oligodendrocytes in multiple sclerosis.
Findings
Lesion stabilization can be achieved by targeting the integrated stress response of oligodendrocytes.
Combining BBB-permeability and stress response therapies prevents lesion formation in the model.
Oligodendrocytes significantly influence tissue recovery under persistent immune activity.
Abstract
Multiple sclerosis (MS) is a neurodegenerative disease in which misdirected, persistent activity of the immune system degrades the protective myelin sheaths of nerve axons. Historically, treatment of MS has relied on disease-modifying therapies that involve immunosuppression, such as targeting of the blood-brain barrier (BBB) to restrict lymphocyte movement. New therapeutic ideas in the development pipeline are instead designed to promote populations of myelin producing cells, oligodendrocytes, by exploiting their innate resilience to the stressors of MS or restoring their numbers. Given the significant advancements made in immunological disease understanding due to mathematical and computational modelling, we sought to develop a platform to (1) interrogate our understanding of the neuroimmunological mechanisms driving MS development and (2) examine the impact of different therapeutic…
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Taxonomy
TopicsNeurogenesis and neuroplasticity mechanisms · Neuroinflammation and Neurodegeneration Mechanisms · Multiple Sclerosis Research Studies