EBV-MS - Targeting Epstein-Barr Virus infection for treatment and prevention of multiple sclerosis

ID Call: HORIZON-HLTH-2023-DISEASE-03 Relationship between infections and non-communicable diseases

Sapienza's role in the project: Other beneficiary

Scientific supervisor for Sapienza: Marco Salvetti 

Department: Neurosciences, Mental Health and Sensory Organs

Project start date: December 1, 2023

Project end date: November 30, 2028

Abstract:

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system. It constitutes the most common non-traumatic cause of neurological impairment among young and middle-aged people and represents a major healthcare burden.The research published in Science in 2022 show that Epstein-Barr virus (EBV) infection greatly increases the risk of developing MS and that is near impossible to develop MS without first being infected by the virus.EBV infection, also known for causing mononucleosis, is very common (more than 95 percent) in the population, but only a small fraction (0.2-0.3 percent) of infected people will develop MS. There is currently no available preventive treatment against EBV infection nor MS.The goal is to develop a new treatment of MS, targeting the underlying driver of the disease rather than downstream consequences. Further, if successful, it will identify people of high risk of developing MS after infection with EBV and give the possibility of primary prevention of the disease in high-risk individuals.This project has the potential to provide mechanistic evidence for EBV being a prerequisite for MS development and progression, which could form the basis for developing strategies to eradicate the disease.. The researchers, representing leading universities and hospitals in Europe and USA, will perform clinical trials of antiviral therapies targeting the EBV infection in MS, analyze blood and saliva samples, and as well perform registry-based research. The group comprises experts in multiple fields, including EBV and human genetics, virology, immunology, neurology, MS, clinical trial design, patient involvement, epidemiology, mathematical modelling, artificial intelligence, data management, as well as multi-stakeholder engagements.

The Sapienza research group, led by Professor Marco Salvetti, will be working on:

• enrichment, amplify, and sequencing of complete EBV genomes from MS individuals from in order to generate a comprehensive catalogue of EBV variants;
• analysis of EBV variabilities (performing EBV-VGWAS) together with the variants of the human donors (from GWAS data) to study whether EBV variability, either by itself or in combination with the host’s affects MS risk, age of onset, the development of the disease, or treatment response;
• genotyping of same cohorts for their HLA alleles and investigation of their potential association with EBV genetic variants and risk of MS.