The role of an Epstein-Barr virus infection in the pathogenesis of multiple sclerosis

Projektinformationen

BEHIND-MS

ID Finanzhilfevereinbarung: 101137235

DOI

10.3030/101137235

EK-Unterschriftsdatum 13 November 2023

Startdatum 1 Dezember 2023

Enddatum 30 November 2028

Finanziert unter

• Health

Gesamtkosten

€ 7 550 708,75

EU-Beitrag

€ 7 550 708,75

Koordiniert durch

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany

Periodic Reporting for period 1 - BEHIND-MS (The role of an Epstein-Barr virus infection in the pathogenesis of multiple sclerosis)

Berichtszeitraum: 2023-12-01 bis 2025-05-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Multiple Sclerosis (MS) is a chronic disease that affects the brain and spinal cord, often leading to disability over time. While treatments can slow the progression, they cannot stop it completely. A major breakthrough came from the discovery that Epstein-Barr virus (EBV) infection is a significant risk factor for MS. The EU-funded BEHIND-MS project aims to understand how EBV triggers MS by studying the virus’ interaction with the immune system in patients. By developing new models and testing treatments, the project hopes to improve diagnosis and therapy options, ultimately reducing the burden of MS on patients and society.

We have established a multidisciplinary team that will for the first time draw a comprehensive map of the interactions between the virus and all arms of the immune system in the blood and brain of patients with MS and how they ultimately lead to neural damage, in the context of genetic risk factors. The team’s expertise span from Neurology, Neurobiology, Pathology, Immunology and Virology to Data science and Bioinformatics. We will also develop an animal model of prodromal MS to identify new pathogenic mechanisms and design new treatment approaches. Finally, we will generate biomarkers to monitor EBV infection in patients with MS.

All of the above will empower the entire healthcare value chain to work towards better clinical management of MS. A detailed understanding of EBV-MS interactions, combined with newly identified biomarkers, and study models will open the doors for researchers, clinicians and industry to capitalize on the mechanisms underlying EBV-MS interactions, and develop new diagnostic, preventive and therapeutic tools and guidelines. Ultimately, by contributing to improved risk analysis, stratification and treatment strategies, BEHIND-MS has the potential to reduce the burden of MS on society.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

During the first 18 months of the project, we have dedicated lot of efforts to the completion of the ethical approvals and to fulfilling legal obligations to exchange biological and human material between institutions across Europe. We have progressed in all WPs and in some cases, this has already led to publication of our results in first tier (Q1) journals.

We have entered a phase of very active patient recruitment to obtain blood samples from patients with MS and healthy controls. These samples are currently being characterized by multiple research groups. Furthermore, we have identified new biomarkers that could possibly facilitate quantification of the Epstein-Barr Virus activity.

We have additionally obtained brain & CSF (cerebrospinal fluid) samples from 8 post-mortem donors and have well progressed in their characterization. In parallel the investigation of potential mechanisms by which EBV may evade the immune system in the brain of patients with MS using tissue samples has been incepted as planned.

We have reprogrammed peripheral blood cells to generate in cells of the nervous system and in blood vessels to study their interactions with EBV and with components of the immune system, as well the vessels that irrigate the brain.

An animal model that reproduces the initial stages of MS has been established and is being currently characterized. This work has also further highlighted a subset of EBV-infected cells as crucial for disease development.

The publicly available BEHIND-MS website (https://www.behind-ms.eu/en/) as well as the BEHIND-MS internal GitLab platform for sharing results has been set-up. Additionally, we are currently developing an AI model for the identification of T-cell receptor (TCRs) and epitopes presented on MHC class II molecules.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The BEHIND-MS project will help understanding how EBV induces the development of MS which may in the long run lead to new diagnostic and therapeutic tools to fight the disease. The project is still at very early stages, but we have already made progress towards this aim.

We will be seeking additional funding from multiple organisations to further develop particularly promising aspects of the project.