Understanding the Epidemiological Connection Between MS and Epstein-Barr Virus: AJ Joshi, MD

WATCH TIME: 3 minutes

"The Nature publication is focusing in on the how. EBV is the leading cause, how is it happening? What it ends up focusing on in that dataset is the molecular mimicry."

Less than a month ago, excitement was generated in the multiple sclerosis (MS) community by research published in Science, which suggested that Epstein-Barr virus (EBV), also known as human herpesvirus 4, may be the leading cause for MS, lending credence to a long-held theory in the field.¹ Shortly after, a second paper extended these findings, by providing a mechanistic basis for how EBV infection can trigger a patient’s immune cells to attack self-tissue in the central nervous system.²

In that study, researchers identified a type of antibody isolated from the cerebrospinal fluid (CSF) of patients with MS, which strongly binds to an EBV protein, EBNA1, and cross-reacts with the central nervous system protein GlialCAM. In a mouse model, the group also demonstrated that immunization with EBNA1 of MS exacerbated the disease and generated a strong antibody response against GlialCAM and EBNA1, enhancing immune cell infiltration and demyelination.

Atara Biotherapeutics has utilized its novel EBV T-cell platform to develop transformative therapies, namely ATA188, to tackle MS at its source. ATA188 targets key epitopes of these antigens, including EBNA1, and has produced positive phase 2 results in patients with progressive MS, a patient population that desperately lacks treatment options. AJ Joshi, MD, chief medical officer, Atara, sat down with NeurologyLive® to discuss the importance of the recently published paper in Nature and how it builds on what clinicians have previously observed.

REFERENCES
1. Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. Published online January 13, 2022. doi:10.1126/science.abj8222

2. New landmark study provides long-sought mechanistic link between EBV and multiple sclerosis, extending findings from recent paper in Science that identified EBV as the leading cause of multiple sclerosis. News release. January 24, 2022. Accessed February 9, 2022. https://www.businesswire.com/news/home/20220122005025/en/New-Landmark-Nature-Study-Provides-Long-Sought-Mechanistic-Link-Between-EBV-and-Multiple-Sclerosis-Extending-Findings-from-Recent-Paper-in-Science-That-Identified-EBV-as-the-Leading-Cause-of-Multiple-Sclerosis