Multiple sclerosis

Multiple Sclerosis Pathways Map

The pathogenesis of multiple sclerosis (MS) involves alterations to multiple pathways and processes, which represent a significant challenge for developing more-effective therapies. Systems biology approaches that study pathway dysregulation should offer benefits by integrating molecular networks and dynamic models with current biological knowledge for understanding disease heterogeneity and response to therapy.

In MS, abnormalities have been identified in several cytokine-signaling pathways, as well as those of other immune receptors. Among the downstream molecules implicated are Jak/Stat, NF-Kb, ERK1/3, p38 or Jun/Fos. MS is likely to be associated with abnormalities in apoptosis/cell death, microglia activation, blood-brain barrier functioning, immune responses, cytokine production, and/or oxidative stress, although which pathways contribute to the cascade of damage and can be modulated remains an open question. While current MS drugs target some of these pathways, others remain untouched, revealing open questions to be studied by applying systems biology approach. Therefore, MS Pathways Map project aims to the development of a comprehensive MS pathways collection, that would represent disease pathogenesis on the different biological levels and would allow researchers to analyze MS data taking into account the information integrated by the domain experts.

The MS map project is led by the group of Pablo Villoslada at August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Spain, and the group of Julio Saez-Rodriguez at RWTH-Aachen University Hospital, Germany.

The project is being built on the network developed by Marti Bernardo in the context of the 7FP EU CombiMS project, with an input from 7FP EU CombiMS consortium members (Saez-Rodriguez et al., PLoS Comput Biol, 2007, PMID 17722974). The network is currently being further refined and extended by Melanie Rinas at the Saez-Rodriguez group in the context of the EraSysMed Sys4MS project.

Related publications

Kotelnikova E, Bernardo-Faura M, Silberberg G, Kiani NA, Messinis D, Melas IN, Artigas L, Schwartz E, Mazo I, Masso M, Alexopoulos LG, Mas JM, Olsson T, Tegner J, Martin R, Zamora A, Paul F, Saez-Rodriguez J, Villoslada P. Signaling networks in MS: a systems-based approach to developing new pharmacological therapies. Mult Scler. 2015 Feb;21(2):138-46. doi: 10.1177/1352458514543339. Epub 2014 Aug 11. PubMed PMID: 25112814.
Malhotra A, Gündel M, Rajput AM, Mevissen HT, Saiz A, Pastor X, Lozano-Rubi R, Martinez-Lapiscina EH, Zubizarreta I, Mueller B, Kotelnikova E, Toldo L, Hofmann-Apitius M, Villoslada P. Knowledge retrieval from PubMed abstracts and electronic medical records with the Multiple Sclerosis Ontology. PLoS One. 2015 Feb 9;10(2):e0116718. doi: 10.1371/journal.pone.0116718. eCollection 2015. PubMed PMID: 25665127.
Gustafsson M, Nestor CE, Zhang H, Barabási AL, Baranzini S, Brunak S, Chung KF, Federoff HJ, Gavin AC, Meehan RR, Picotti P, Pujana MÀ, Rajewsky N, Smith KG, Sterk PJ, Villoslada P, Benson M. Modules, networks and systems medicine for understanding disease and aiding diagnosis. Genome Med. 2014 Oct 17;6(10):82. doi: 10.1186/s13073-014-0082-6. PubMed PMID: 25473422.
Saez-Rodriguez J, Simeoni L, Lindquist JA, Hemenway R, Bommhardt U, Arndt B, Haus UU, Weismantel R, Gilles ED, Klamt S, Schraven B. A logical model provides insights into T cell receptor signaling. PLoS Comput Biol. 2007 Aug;3(8):e163. Epub 2007 Jul 5. PubMed PMID: 17722974

Development Team

	Julio Saez-Rodriguez, PhD Heidelberg University Hospital, Heidelberg, Germany Professor of Medical Bioinformatics and Data Analysis
	Ekaterina Kotelnikova, PhD August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Spain Head of Immune Systems Biology Group; Founder and Scientific Advisor at Personal Biomedicine, Inc.
	Melanie Rinas, PhD RWTH-Aachen University Hospital, Aachen, Germany Postdoctoral Researcher in Computational Biomedicine
	Gemma Vila, BSc August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Spain Scientist
	Pablo Villoslada, MD August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Spain Director of the MS pathogenesis and therapeutics Group at IDIBAPS; Adjunct Professor at the Department of Neurology, University of California, San Francisco (UCSF); National Coordinator of the Spanish Network of Excellence in Multiple Sclerosis (REEM), Instituto de Salud Carlos III; Member of the Scientific Advisory Board of the International Society of Neuroimmunology

Editorial Panel (Domain Experts)

Pablo Villoslada, MD
August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Spain
Director of the MS pathogenesis and therapeutics Group at IDIBAPS; Adjunct Professor at the Department of Neurology, University of California, San Francisco (UCSF); National Coordinator of the Spanish Network of Excellence in Multiple Sclerosis (REEM), Instituto de Salud Carlos III; Member of the Scientific Advisory Board of the International Society of Neuroimmunology

Irati Zubizarreta, MD
August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Spain
Neurologist