When I posted the link to our EBV and MS meta-analysis on social media yesterday I was taken to task because of the slow progress we have made in MS prevention.
Why has no preventative action been taken yet? What are they waiting for? I have had MS for more than 50 years and in all those decades the Epstein- Barr virus has been a usual suspect over and over and over again. Had glandular fever very badly aged 15. Not been well since.— Judy Graham (@jdyghm) September 30, 2019
Can I remind you that science moves steadily and slowly and the biggest problem we have is the slow adoption, or rejection, of innovations or new ideas.
“The human mind treats a new idea the same way the body treats a strange protein; it rejects it.”
Peter Medawar, Nobel prize laureate, in Physiology or Medicine, 1960.
I was convinced by the evidence already back in 1999 that EBV was the likely cause of MS. I have been working on EBV ever since and the progress has been very slow. The main reason I left the Institute of Neurology (Queen Square) was to move to a multi-disciplinary institute, that would allow me space and time to work on EBV. However, it takes more than just moving to a new research environment to build momentum around a new research hypothesis.
I have had more grant applications rejected around the viral hypothesis of MS than I care to count. It is very depressing. Despite this, we are pushing on slowly with our plans to create a trial-ready cohort of people at high risk of MS for exploratory MS prevention studies. Dr Ruth Dobson is doing quite an amazing job at getting this off the ground. We are also pushing forward with our ideas around treating MS with antivirals that target EBV. To say that the funding for doing these trials has been difficult is an understatement, but I am hoping if we can get pilot data we can convince the sceptics to fund definitive trials.
We are also not the only team working on the EBV hypothesis of MS. Michael Pender in Brisbane, Australia, is doing great things and Atara Bio has taken up the baton in industry. I have recently posted on their preliminary results that were presented at ECTRIMS.
I spend most of my waking day doing MS and a large part of that is thinking about EBV and MS prevention. The main strand of MS prevention is an EBV vaccination study. The vaccine is not in our hands, but the capable hands of Jeff Cohen at the NIH, and hopefully a deep-pocketed Pharma company to commercialise it. Even if we get an effective EBV vaccine developed and launched we will still have to overcome the public resistance to vaccination and to convince public health officials that this is a worthy idea.
The battles ahead are numerous, but we will get there in the end. We have to. We don’t want the next generation of MSers asking us why we haven’t done anything to prevent MS given the current state of knowledge.
EBV is almost certainly the cause of MS. What are we doing about it?
Background: EBV infection is thought to play a central role in the development of Multiple Sclerosis (MS). If causal, it represents a target for interventions to reduce MS risk.
Objective: To examine the evidence for interaction between EBV and other risk factors, and explore mechanisms via which EBV infection may influence MS risk.
Methods: Pubmed was searched using the terms multiple sclerosis AND Epstein Barr virus, multiple sclerosis AND EBV, clinically isolated syndrome AND Epstein Barr virus and clinically isolated syndrome AND EBV. All abstracts were reviewed for possible inclusion.
Results: 262 full-text papers were reviewed. There was evidence of interaction on the additive scale between anti-EBV antibody titre and HLA genotype (AP 0.48, p<1×10-4; RERI 3.84, p<5×10-3; S 1.68, p=0.06). Previous IM was associated with increased OR of MS in HLA-DRB1*1501 positive but not HLA-DRB1*1501 negative persons. Smoking was associated with a greater risk of MS in those with high anti-EBV antibodies (OR 2.76) but not low anti-EBV antibodies (OR 1.16). No interaction between EBV and risk factors was found on a multiplicative scale.
Conclusions: EBV appears to interact with at least some established MS risk factors. The mechanism via which EBV influences MS risk remains unknown.