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Open AccessArticle

The Potential of Computational Modeling to Predict Disease Course and Treatment Response in Patients with Relapsing Multiple Sclerosis

1
Department of Drug Sciences, University of Catania, 95125 Catania, Italy
2
Department of Mathematics and Computer Science, University of Catania, 95125 Catania, Italy
3
National Research Council of Italy, 00185 Rome, Italy
4
Multiple Sclerosis Center, Neurology Unit, Garibaldi Hospital, 95124 Catania, Italy
*
Author to whom correspondence should be addressed.
The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.
Cells 2020, 9(3), 586; https://doi.org/10.3390/cells9030586
Received: 13 January 2020 / Revised: 26 February 2020 / Accepted: 27 February 2020 / Published: 1 March 2020
(This article belongs to the Special Issue Quantitative Models of Autoimmunity)
As of today, 20 disease-modifying drugs (DMDs) have been approved for the treatment of relapsing multiple sclerosis (MS) and, based on their efficacy, they can be grouped into moderate-efficacy DMDs and high-efficacy DMDs. The choice of the drug mostly relies on the judgment and experience of neurologists and the evaluation of the therapeutic response can only be obtained by monitoring the clinical and magnetic resonance imaging (MRI) status during follow up. In an era where therapies are focused on personalization, this study aims to develop a modeling infrastructure to predict the evolution of relapsing MS and the response to treatments. We built a computational modeling infrastructure named Universal Immune System Simulator (UISS), which can simulate the main features and dynamics of the immune system activities. We extended UISS to simulate all the underlying MS pathogenesis and its interaction with the host immune system. This simulator is a multi-scale, multi-organ, agent-based simulator with an attached module capable of simulating the dynamics of specific biological pathways at the molecular level. We simulated six MS patients with different relapsing–remitting courses. These patients were characterized based on their age, sex, presence of oligoclonal bands, therapy, and MRI lesion load at the onset. The simulator framework is made freely available and can be used following the links provided in the availability section. Even though the model can be further personalized employing immunological parameters and genetic information, we generated a few simulation scenarios for each patient based on the available data. Among these simulations, it was possible to find the scenarios that realistically matched the real clinical and MRI history. Moreover, for two patients, the simulator anticipated the timing of subsequent relapses, which occurred, suggesting that UISS may have the potential to assist MS specialists in predicting the course of the disease and the response to treatment. View Full-Text
Keywords: computational modeling; agent-based modeling; systems biology; multiple sclerosis; immunity; degenerative disease computational modeling; agent-based modeling; systems biology; multiple sclerosis; immunity; degenerative disease
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MDPI and ACS Style

Pappalardo, F.; Russo, G.; Pennisi, M.; Parasiliti Palumbo, G.A.; Sgroi, G.; Motta, S.; Maimone, D. The Potential of Computational Modeling to Predict Disease Course and Treatment Response in Patients with Relapsing Multiple Sclerosis. Cells 2020, 9, 586.

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