Thank you so much for all your incredibly helpful and well presented information, including this. I am a newly diagnosed medic (Barts alum too!) just waiting to start Ocrevus, and have found it a complete minefield being on the other side. I have been particularly worried about what to do re: the risk to my 3 daughters (aged 10, 14 & 16); this answers all my questions, which is great. It means so much to see someone in your position so clearly positively and passionately advocating for your patients, it gives us great hope. We're happy to join in with trials to help - feel it's our duty. Very excited about all the EBV work and hopeful that the vaccine trial is fruitful!
Two queries….. firstly do we need K2 as well as vitamin D for it to be worthwhile taking and secondly is there anywhere currently we can register our child’s interest in being part of a trial or do we, more likely, need to await, a vaccine and study? Lol….. I know I’m jumping ahead!!
Ebv is very common about a 90% worldwide because there are many kinds. People who develop ms during their lifetime is probably around 1% worldwide. To relate them the way you do is actually kinda irresponsible. The right way to pit it is just a 32 higher chance of getting it in your lifetime. My whole husbands family has had ebv or some type of it. None of them have ms. And their ages range from 20s-70s. I believe it might be a first condition but followed by many other triggers to finally get ms.
Yes, but MS is only one disease caused by EBV. Preventing EBV infection will prevent IM, which is disabling in itself, but may prevent close to 1% of human cancers and several autoimmune diseases.
Yes, MS is a rare manifestation of a common exposure, but that doesn't nullify the observation that people who don't get infected with EBV don't get MS. The issue is that you can prevent yourself getting infected with EBV at the moment. In the future hopefully a vaccine will be able to do this.
Makes sense, i was diagnosed with ms after being perfectly healthy, 3-4 months after my partner had terrible glandular fever. I initially tested negative for ebv but when i had proper virology carried out recently for hsct it was positive. I actually commented on one of the posts on the old blog and you did tell me i would likely be positive if proper testing was carried out.
Many viruses transactivate EBV, i.e. wake it up from its dormancy to cause lytic infection. As EBV is a well known cause of post-viral fatigue it may be contributing to long-COVID. EBV is currently being investigated as a cause/contributor to the fatigue associated with long-COVID. It is too early to tell whether or not treating or targeting EBV reactivation will help patients with long-COVID fatigue.
Very interesting, I was trying to understand that Q too.
- Is EBV dormant and then reawakens via a second virus? - but only some people based on presumably other factors that impact their immune system?
- Or are the neurofilaments there from the start of EBV infection in just those susceptible individuals who will then go on to have MS?
- Or, are other viruses and stresses/changes in the immune system simply aggravating the invisible smouldering MS present from the EBV infection maybe decades before, and then the additional factors create the scenario where it suddenly becomes apparent as the start of the disease we can then diagnose?
Hope those Q’s don’t sound silly, just trying to understand 🤩
Thank you again Prof G - if there are and fundraising activities for continuing your work on this, we could all rally together?
Jan 13, 2022·edited Jan 13, 2022Liked by Gavin Giovannoni
Thank you for sharing this.
I remember that when I was firstly diagnosed with MS in 2017 I immediately started searching for information online, and one of the first articles I stumbled across for some reason was one about the MS incidence in the Faroe islands and the theory of it being introduced via an ‘infectious agent’ in the ‘40s by English troops.
It’s interesting how a ‘random’ and fairly ‘anorthodox’ (as it was not proven) concept of MS as an epidemic that I came across as a naive patient back then might hold quite a bit of truth(?) And of course quickly after I also came across EBV as a theory.
Another thing I remember from my diagnosis was being explained by the doctor while in the hospital that ‘the immune cells go in the brain’ and then my first question was ‘how do make sure we get them out of the brain?’ A very basic question, but it seems so interestingly relevant, after observing now the discussion about how we can optimise treatment for BBB penetration.
This makes me think about the concept of ‘fresh perspectives’ being introduced into MS research. If most evidence is there in front of our eyes, how could we introduce as many new competent people into MS research that can see things for what they are and ‘get it done’?
What is missing? Is it the right people who can quickly come up with intelligent research designs and potential curative/preventive agents? Because you seem to be one of those. So then is it lobbying? Is it knowing the right people in pharma that have the power to move the needle? I wish with all my heart that I could personally contribute to MS being cured, I am just not sure how I could do that.
We have been trying for close to two decades to get CNS penetrant anti-EBV trials off the ground. I agree with you and think we need to purge the CNS of B-cells and plasma cells that may harbour EBV. This is why we are doing the SIZOMUS study. If you live in London or close to London please volunteer to participate in the SIZOMUS trial.
Yes the SIZOMUS, https://clinicaltrials.gov/ct2/show/NCT03783416 has the status as not yet recruiting so I hadn't really considered it just yet, was keeping an eye on the status. Should we get in touch with Dr Gnanapavan if we want to be considered? Many thanks
I can connect the dots of infectious Mono to my MS diagnosis by association, perhaps give insight into the catalyst of what triggered my MS attacks.
I was one to run to the fires, I presumed I was handling stress well, but learned stress takes no prisoners.
My two major MS attacks were during the highest stressors of my life, i was accustomed to moderate stress daily as a medical professional in a busy office.
However, I experienced periods of extreme high stress not ever experienced, then MS attacked in 2010 and 2013.
I contribute the two attacks to poor sleeping duration due to constant high stress at work/home.
Since then, i've learned to reduce stress and go slow in life or you lose.
My legs have rebounded, I'm still walking in my mid fifties, but the damage was done. Thankfully, no other attacks since 2013. I stopped working in 1-1-2020, fortuitous timing saved me from covid hell at the hospital, and the high stress. The hot summers worsen my MS, I can barely move after working outside in the heat for 3 hours vs 8 hours in the cold I don't worsen, I've learned I need to move to a cooler life.
I was infected with severe infectious mononucleosis at age 14, hitting me after a week long basketball camp where I wore my self out physically. `
I couldn't swallow resulting in dehydration in the hospital for 4 days, then years later my life changed. I recall abnormal fatigue in my late teen years, then especially after 7 long years of college, the fatigue worsened after graduation.
My mother had MS as well and older brother has MS, but won't get diagnosed.
Will a EBV vaccine help MSers like already partially damaged or not ?
Re the vaccine. I don't know. But there is a strong rationale to test a therapeutic vaccine as a treatment for MS. By boosting immunity to EBV it may help control the virus and hence control MS.
Thank you so much for all your ideas about the cause of MS and the reasons why. Is there any way that MS could be caused by two different things for example the EBV and a trigger and something started before birth caused possibly by low folic acid and/or low Vit B12? I am only asking because of the number of different symptoms that people have. Some people like the cold whereas others like the heat and some people's MS like altitude and others like the hyperbaric oxygen chamber. All these different reactions/side effects for one illness?
Thank you so much for everything you have done and are doing to help us.
Yes, EBV is necessary but not sufficient and other factors play a role in triggering the disease. However, it looks as if the other factors only count if EBV is present.
Dear Professor Giovannoni, So it seems evident that EBV must be present in order to develop MS. Do you know when Oligoclonal bands actually develop? For example, an individual diagnosed with EBV/Mono at age ~16, and then a diagnosis of MS at age ~28. Where along the way do these bands develop? And why is the presence of these bands such a mystery in MS research? Thank you for everything you do!! Truly, you are paving the way to discovering the causation of MS.
The oligoclonal bands are usually present at diagnosis and hence must be there years before symptoms emerge. In the small number of OCB-ve pwMS when they have a lumbar puncture in 6-12 months about half will have developed them. Please note it is not essential to have OCBs to be diagnosed with MS.
Thank you for this explanation--It absolutely makes sense. In your opinion, could it be possible to develop the Oligoclonal bands from the actual EBV infection? Or would development of these bands most likely be caused from various other precipitating pathologies? Since the bands "must be there years before symptoms emerge", makes me ponder whether they somehow occur as a result of the EBV, since the EBV typically occurs years before an official MS dx is made.
Is there a correlation with a higher EBV IGG titer and causation of MS? Meaning if you have a lower IGG is the likelihood to cause MS less than people with a higher titer level?
Thank you for the encouragement to be more active in advocating for this. i think we forget as patients sometimes how important it is to advocate for all PwMS / + at risk family while we are caught up dealing with all the other stuff that comes our way. I was very happy to read Moderna had its first trial participant dosed this month for its EBV vax. Here's hoping its a winner.
Do you think any EBV expressed membrane proteins could be targeted by monoclonal antibodies which would be more specific to EBV infected B cells than anti-CD20?
Thx for caring for pwMS. Suppose a jab is developed, who should get it? Should it be integrated in national vaccination programs? Will it be cheap enough?
My hope is the new Quantum super computers coming online by IBM/others will solve the MS riddle. The powerful quantum computers plus the AI will hopefully solve the MS riddle, been 200 years since MS was first documented.
It will be hard to convince politics to mass vaccinate all people against EBV considering 90% seroprevalence + low MS incidence, even considering other malignancies and diseases, they probably wont find it cost beneficial. Shouldn't the first step in your longterm MS prevention strategy be getting funds for development of cheap genetic screening tests?
Not sure that will help. Most people with the highest genetic risk will not get the disease.
Even if you are a female identical twin with a sister who has MS your chances of getting the disease are only about 30% in high-risk countries like the UK, Nordic countries and Canada. In lower risk southern European countries the risk falls to about 8.5%.
Are there other blockers to starting a vaccine trial or simply put, do we, as an MS Community, need to find a way to raise the money to fund it, and if so how much?
Main blocker is a lack of a vaccine, but this may change. The big issue is doing a vaccine trial in the general population to prevent IM and/or targeting people at high-risk of getting MS. The first option will take decades to give us an answer on MS prevention. The high-risk study needs the MS community to do it and this then requires us to convince the community to fund the trial.
As a mother who has MS, I would be keen for my daughter to participate given the possibility to improve those 1 in 40 odds for her. I guess it's about finding a way to give enough people the knowledge of the possibility so they can choose to engage and register interest. Of which I guess sharing this information is the first step, so thankyou.
We are hoping to start a register of high-risk family members to prepare a vaccine-ready trial cohort. Would you be interested to let your daughter participate?
Hi Prof G, my 82 year old father was diagnosed with PPMS in 2018. The idea of heritability is obviously concerning and I understand the limitations in what is currently possible. Would you be recommending the vit d3 protocol for my 16 year daughter - would there be any downside?
Thank you so much for all your incredibly helpful and well presented information, including this. I am a newly diagnosed medic (Barts alum too!) just waiting to start Ocrevus, and have found it a complete minefield being on the other side. I have been particularly worried about what to do re: the risk to my 3 daughters (aged 10, 14 & 16); this answers all my questions, which is great. It means so much to see someone in your position so clearly positively and passionately advocating for your patients, it gives us great hope. We're happy to join in with trials to help - feel it's our duty. Very excited about all the EBV work and hopeful that the vaccine trial is fruitful!
Thank you.
Is the incidence of MS higher in people that developed ACTIVE Mononucleosis as a child than those that didn't.
Yes, 2.0-2.5x higher.
Professor G, thanks so much for this post. I was very sick with infectious mononucleosis at 16 and missed six weeks of school.
After years of symptoms, I wasn’t diagnosed with MS until I was 57.
I had Mononucleosis at about 13 years old, dxd at 22, 50 now
This is very interesting; I too had mono aged 11 and was off school for 5 weeks.
I have antibodies for EBV, but never remember having had mono. Diagnosed with MS at 49.
In high income countries only 30% of EBV positive people have a history of IM. I low and middle income countries this figure is much lower.
Two queries….. firstly do we need K2 as well as vitamin D for it to be worthwhile taking and secondly is there anywhere currently we can register our child’s interest in being part of a trial or do we, more likely, need to await, a vaccine and study? Lol….. I know I’m jumping ahead!!
I am not aware of any MS-specific data that supports taking K2 with vD for MS-related reasons.
Ebv is very common about a 90% worldwide because there are many kinds. People who develop ms during their lifetime is probably around 1% worldwide. To relate them the way you do is actually kinda irresponsible. The right way to pit it is just a 32 higher chance of getting it in your lifetime. My whole husbands family has had ebv or some type of it. None of them have ms. And their ages range from 20s-70s. I believe it might be a first condition but followed by many other triggers to finally get ms.
Yes, but MS is only one disease caused by EBV. Preventing EBV infection will prevent IM, which is disabling in itself, but may prevent close to 1% of human cancers and several autoimmune diseases.
Yes, MS is a rare manifestation of a common exposure, but that doesn't nullify the observation that people who don't get infected with EBV don't get MS. The issue is that you can prevent yourself getting infected with EBV at the moment. In the future hopefully a vaccine will be able to do this.
Makes sense, i was diagnosed with ms after being perfectly healthy, 3-4 months after my partner had terrible glandular fever. I initially tested negative for ebv but when i had proper virology carried out recently for hsct it was positive. I actually commented on one of the posts on the old blog and you did tell me i would likely be positive if proper testing was carried out.
there are people that say that post covid there was activation of EBV….do you have any experience/evidence regarding MS activation?
seems more and more coming your way doc!:
statnews.com/2022/01/13/strong-new-evidence-suggests-virus-triggers-multiple-sclerosis/
and there might be hope:
https://science.sciencemag.org/content/371/6525/145.full
Many viruses transactivate EBV, i.e. wake it up from its dormancy to cause lytic infection. As EBV is a well known cause of post-viral fatigue it may be contributing to long-COVID. EBV is currently being investigated as a cause/contributor to the fatigue associated with long-COVID. It is too early to tell whether or not treating or targeting EBV reactivation will help patients with long-COVID fatigue.
Very interesting, I was trying to understand that Q too.
- Is EBV dormant and then reawakens via a second virus? - but only some people based on presumably other factors that impact their immune system?
- Or are the neurofilaments there from the start of EBV infection in just those susceptible individuals who will then go on to have MS?
- Or, are other viruses and stresses/changes in the immune system simply aggravating the invisible smouldering MS present from the EBV infection maybe decades before, and then the additional factors create the scenario where it suddenly becomes apparent as the start of the disease we can then diagnose?
Hope those Q’s don’t sound silly, just trying to understand 🤩
Thank you again Prof G - if there are and fundraising activities for continuing your work on this, we could all rally together?
Thank you for sharing this.
I remember that when I was firstly diagnosed with MS in 2017 I immediately started searching for information online, and one of the first articles I stumbled across for some reason was one about the MS incidence in the Faroe islands and the theory of it being introduced via an ‘infectious agent’ in the ‘40s by English troops.
It’s interesting how a ‘random’ and fairly ‘anorthodox’ (as it was not proven) concept of MS as an epidemic that I came across as a naive patient back then might hold quite a bit of truth(?) And of course quickly after I also came across EBV as a theory.
Another thing I remember from my diagnosis was being explained by the doctor while in the hospital that ‘the immune cells go in the brain’ and then my first question was ‘how do make sure we get them out of the brain?’ A very basic question, but it seems so interestingly relevant, after observing now the discussion about how we can optimise treatment for BBB penetration.
This makes me think about the concept of ‘fresh perspectives’ being introduced into MS research. If most evidence is there in front of our eyes, how could we introduce as many new competent people into MS research that can see things for what they are and ‘get it done’?
What is missing? Is it the right people who can quickly come up with intelligent research designs and potential curative/preventive agents? Because you seem to be one of those. So then is it lobbying? Is it knowing the right people in pharma that have the power to move the needle? I wish with all my heart that I could personally contribute to MS being cured, I am just not sure how I could do that.
We have been trying for close to two decades to get CNS penetrant anti-EBV trials off the ground. I agree with you and think we need to purge the CNS of B-cells and plasma cells that may harbour EBV. This is why we are doing the SIZOMUS study. If you live in London or close to London please volunteer to participate in the SIZOMUS trial.
Do you have an idea of when you will start recruiting for the study? Thanks for this post.
Which study? The SIZOMUS is recruiting now. The vaccine study is waiting for an effective EBV vaccine.
Yes the SIZOMUS, https://clinicaltrials.gov/ct2/show/NCT03783416 has the status as not yet recruiting so I hadn't really considered it just yet, was keeping an eye on the status. Should we get in touch with Dr Gnanapavan if we want to be considered? Many thanks
Yes, please.
Prof G,
I can connect the dots of infectious Mono to my MS diagnosis by association, perhaps give insight into the catalyst of what triggered my MS attacks.
I was one to run to the fires, I presumed I was handling stress well, but learned stress takes no prisoners.
My two major MS attacks were during the highest stressors of my life, i was accustomed to moderate stress daily as a medical professional in a busy office.
However, I experienced periods of extreme high stress not ever experienced, then MS attacked in 2010 and 2013.
I contribute the two attacks to poor sleeping duration due to constant high stress at work/home.
Since then, i've learned to reduce stress and go slow in life or you lose.
My legs have rebounded, I'm still walking in my mid fifties, but the damage was done. Thankfully, no other attacks since 2013. I stopped working in 1-1-2020, fortuitous timing saved me from covid hell at the hospital, and the high stress. The hot summers worsen my MS, I can barely move after working outside in the heat for 3 hours vs 8 hours in the cold I don't worsen, I've learned I need to move to a cooler life.
I was infected with severe infectious mononucleosis at age 14, hitting me after a week long basketball camp where I wore my self out physically. `
I couldn't swallow resulting in dehydration in the hospital for 4 days, then years later my life changed. I recall abnormal fatigue in my late teen years, then especially after 7 long years of college, the fatigue worsened after graduation.
My mother had MS as well and older brother has MS, but won't get diagnosed.
Will a EBV vaccine help MSers like already partially damaged or not ?
Re the vaccine. I don't know. But there is a strong rationale to test a therapeutic vaccine as a treatment for MS. By boosting immunity to EBV it may help control the virus and hence control MS.
Thank you so much for all your ideas about the cause of MS and the reasons why. Is there any way that MS could be caused by two different things for example the EBV and a trigger and something started before birth caused possibly by low folic acid and/or low Vit B12? I am only asking because of the number of different symptoms that people have. Some people like the cold whereas others like the heat and some people's MS like altitude and others like the hyperbaric oxygen chamber. All these different reactions/side effects for one illness?
Thank you so much for everything you have done and are doing to help us.
Yes, EBV is necessary but not sufficient and other factors play a role in triggering the disease. However, it looks as if the other factors only count if EBV is present.
Dear Professor Giovannoni, So it seems evident that EBV must be present in order to develop MS. Do you know when Oligoclonal bands actually develop? For example, an individual diagnosed with EBV/Mono at age ~16, and then a diagnosis of MS at age ~28. Where along the way do these bands develop? And why is the presence of these bands such a mystery in MS research? Thank you for everything you do!! Truly, you are paving the way to discovering the causation of MS.
The oligoclonal bands are usually present at diagnosis and hence must be there years before symptoms emerge. In the small number of OCB-ve pwMS when they have a lumbar puncture in 6-12 months about half will have developed them. Please note it is not essential to have OCBs to be diagnosed with MS.
Thank you for this explanation--It absolutely makes sense. In your opinion, could it be possible to develop the Oligoclonal bands from the actual EBV infection? Or would development of these bands most likely be caused from various other precipitating pathologies? Since the bands "must be there years before symptoms emerge", makes me ponder whether they somehow occur as a result of the EBV, since the EBV typically occurs years before an official MS dx is made.
Is there a correlation with a higher EBV IGG titer and causation of MS? Meaning if you have a lower IGG is the likelihood to cause MS less than people with a higher titer level?
Not that I am aware of. The link between higher risk of MS is high levels of anti-EBNA1 and anti-EBNA complex antibodies and not total IgG.
Thank you for the encouragement to be more active in advocating for this. i think we forget as patients sometimes how important it is to advocate for all PwMS / + at risk family while we are caught up dealing with all the other stuff that comes our way. I was very happy to read Moderna had its first trial participant dosed this month for its EBV vax. Here's hoping its a winner.
Do you think any EBV expressed membrane proteins could be targeted by monoclonal antibodies which would be more specific to EBV infected B cells than anti-CD20?
Unfortunately, not. The latency associated proteins are intracellular.
Dear Prof G
Thx for caring for pwMS. Suppose a jab is developed, who should get it? Should it be integrated in national vaccination programs? Will it be cheap enough?
All these questions will get answered in time. It will take years of research to answer many of these questions.
My hope is the new Quantum super computers coming online by IBM/others will solve the MS riddle. The powerful quantum computers plus the AI will hopefully solve the MS riddle, been 200 years since MS was first documented.
It will be hard to convince politics to mass vaccinate all people against EBV considering 90% seroprevalence + low MS incidence, even considering other malignancies and diseases, they probably wont find it cost beneficial. Shouldn't the first step in your longterm MS prevention strategy be getting funds for development of cheap genetic screening tests?
Not sure that will help. Most people with the highest genetic risk will not get the disease.
Even if you are a female identical twin with a sister who has MS your chances of getting the disease are only about 30% in high-risk countries like the UK, Nordic countries and Canada. In lower risk southern European countries the risk falls to about 8.5%.
Genetic risk is only a small part of the puzzle.
Thankyou for making this so clear.
Are there other blockers to starting a vaccine trial or simply put, do we, as an MS Community, need to find a way to raise the money to fund it, and if so how much?
Main blocker is a lack of a vaccine, but this may change. The big issue is doing a vaccine trial in the general population to prevent IM and/or targeting people at high-risk of getting MS. The first option will take decades to give us an answer on MS prevention. The high-risk study needs the MS community to do it and this then requires us to convince the community to fund the trial.
As a mother who has MS, I would be keen for my daughter to participate given the possibility to improve those 1 in 40 odds for her. I guess it's about finding a way to give enough people the knowledge of the possibility so they can choose to engage and register interest. Of which I guess sharing this information is the first step, so thankyou.
We are hoping to start a register of high-risk family members to prepare a vaccine-ready trial cohort. Would you be interested to let your daughter participate?
Absolutely, yes please.
I would also be happy to share details with various online groups for pwms if that was helpful with details of where to register interest.
Hi Prof G, my 82 year old father was diagnosed with PPMS in 2018. The idea of heritability is obviously concerning and I understand the limitations in what is currently possible. Would you be recommending the vit d3 protocol for my 16 year daughter - would there be any downside?
Yes, I recommend we all take vD supplements with a few medical exceptions. Yes, it is safe.