I’ve ended up learning a lot about multiple sclerosis (MS) while writing The Niche for the past twelve plus years, but I’ve never seen anything like the new research linking EBV and MS. EBV stands for Epstein Barr Virus.
The reason I’ve learned much more about MS while writing here is that there has been so much interest in using stem cells for MS. One of the criticisms about the idea of using cell therapy for MS has been that we didn’t have a good handle on what causes MS. So how to treat it if you don’t know the cause? You can try to target the key immunological component. In that sense the rationale for using cells against MS has been a postulated cellular function reducing the autoimmunity that is key to MS.
So what’s the story on the new research on the cause of MS?
EBV and MS
The new research much more strongly linking EBV and MS provides a major step forward in understanding why MS happens in the first place. The paper is Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis in Science.
The research reports that for many patients who ultimately get MS it is preceded by an EBV infection. In fact, this may be true of almost every case of MS. The team identified 801 new cases of MS and 800 were at some point positive for EBV. That leaves only one other case untied to EBV, which is remarkable.
The new study reports that EBV infection confers a 32-fold increased risk of MS as well. Further, only after EBV was detectable in new patients did markers of neuron damage appear. Such factors can be hallmarks of early MS.
Infections with other viruses like CMV were not associated with MS in the study.
The authors also make a strong case to rule out other factors, like certain genetic states, besides EBV that could have confounded their findings. For instance, the strongest known genetic factor linked to MS, having two copies of the HLA-DR15 allele, only confers a 3-fold increased risk of MS. That’s hardly enough to explain the thirty-plus-fold risk associated with EBV.
How could EBV trigger MS?
So what’s the link with EBV? One major possibility is that some of the virus’ proteins are similar to human myelin proteins that stud the outside of our neurons. Along this line of thinking, during an EBV infection the immune system goes after EBV proteins and neurons end up subject to friendly immune fire.
Some immune cells that are essentially forever infected with EBV could cause problems too.
Research over many years has documented an accumulation of EBV+ B cells in the brains of MS patients. They could live there and damage neurons.
MS treatments and prevention
I mentioned the idea of using stem cells to treat MS. It’s still experimental.
Current established treatments for MS are less than ideal for some patients and awful in certain cases. The main goal of such treatments has been to tamp down the auto-immune response. Immunosuppressants can have many side effects.
It is for these reasons that so many people have been excited about the idea of stem cells for MS. Maybe they’d work and be less toxic? So far, the use of stem cells or other cellular products like MSCs alone does not look so promising. However, what has been very encouraging are data on a combination of certain types of chemo ablation of the auto-reactive immune system followed by a hematopoietic stem cell transplant.
The EBV connection opens up the possibility that targeting EBV could eliminate MS from the population. Perhaps the most exciting idea is that EBV vaccination could prevent most cases of MS by blocking EBV infection in the first place.
Several groups are exploring this idea and Moderna is starting to test an RNA vaccine against EBV.
The EBV link could also lead to new treatments to very specifically target immune cells that are the most problematic.
It still could be a long road ahead but there’s real reason for hope on MS. The other important point here is that a possible vaccine against EBV could made huge impact via preventing EBV-related Burkitt lymphoma in some countries.
The connection with EBV may be why i and many others have had success with Apheresis in significantly modulating the MS disease process.
I suspect we will start seeing many more connections between infectious diseases and these types of chronic conditions.
Microbiome may also be involved here I suspect
Thank you for bringing attention to this important correlation
But, Paul, since almost every adult has had an EBV infection, such a condition, though it might be necessary cannot be sufficient. If it is, indeed, a necessary condition, a universal and universally vaccine against EBV should be helpful. (Good luck, with the science and with the public acceptance of something that reduces your risk of MS from, say 0.35% (population prevalence) to 0.001% (never zero), what kind of uptake do you think you’d get? Maybe sell it as a prevention to mononucleosis (common result of EBV infection) or perhaps Burkitt’s Lymphoma (not rare reaction at least in East Africa). And, of course, knowing that it is necessary could lead to some good scientific leads for figuring out what’s going on – and what else has to happen to cause disease (and implicitly could be prevented to provide protection). But my own sense (which could be wrong) was that people got too excited about this finding. Thoughts?
Hi Hank,
You raise some good points as usual. Yes, the mono and especially the Burkitt part of the EBV story could be valuable for marketing such a possible future vaccine. I also wonder about EBV contributing to other diseases too that we just don’t know about very clearly yet.
It’s possible the EBV connection to MS could lead to a new treatment and not just prevention measures. That might be more practical than the vaccine angle in some countries but in other places like those with lots of Burkitt the vaccine could be a huge deal. I should have mentioned that in my post so I’ve now added it in. I guess one other point is that the link between MS and EBV has been known for a long time, and this new paper just nailed it down a lot more clearly than before so it’s not like it’s an entirely new idea so maybe there was some overexuberance on the new pub by some of us.