After laying out a controversial model for the role of EBV in MS, Gavin Giovannoni went a step further in this year’s Whitaker Lecture, suggesting a cure for MS could be on the horizon. Building on the evidence from last year’s epidemiological study of the US Military, which found EBV seroconversion is all but required for developing MS, Giovannoni laid out evidence suggesting the virus is the driver of demyelinating events in MS.
Giovannoni argued that the effects of many treatments for MS might be attributable to mitigating the effects of latent EBV. For example, sequestration of memory B-cells to lymph nodes by fingolimod or their depletion by ocrelizumab have been proposed to assist patients with MS by preventing their participation in an autoimmune response. However, their effects could also be due to prevention of EBV-laden memory B-cell from entering the CNS and introducing reactivated virus.
If EBV infection is an essential prerequisite for MS, one of the many anti-EBV vaccines under development may eventually provide a tool for broadly preventing MS. The biggest splash, however, came from the suggestion that this new, EBV-based model might point to a cure for MS. While the role for the anti-CD40L agent frexalimab has been proposed as blocking the co-stimulation of T-cells by other immune cells, it may also be preventing EBV from using CD40L to promote transformation and survival of infected B-cells. (See our post on DMTs for his thoughts on how BTK inhibitors could reduce the effects of EBV.) For the full slide deck from his presentation, click here.
Other roles for EBV?
Broader acceptance of the link between EBV and MS, however, does not necessarily mean broader acceptance of the mechanisms of action proposed by Dr. Giovannoni. At our most recent researchXchange Live event, Jessica Allanach and Dr. Marc Horwitz discussed their work studying the effects of EBV in a mouse model of MS, with results that argue for a very different model of EBV’s role. For the full slide deck, with the opportunity to further discuss the presentation, click here.
A video of the event including a lively discussion with Steve Jacobson of NIH and Mike Racke of Quest Diagnostics can be found here. Look for our interviews with the presenters and Dr. Jacobson on the critical question of EBV in MS in the coming weeks.
Further reading:
Epstein–Barr virus and multiple sclerosis. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362539/
What do animal models tell us about the role of EBV in the pathogenesis of multiple sclerosis? https://www.frontiersin.org/articles/10.3389/fimmu.2022.1036155/full
Find a Zotero library with these manuscripts here.
