What is the most exciting MS research on the horizon?

I was asked about which paper I have written or co-written that has or will have the most impact in the field of MS. There is little doubt that it is our report of our 2017 workshop on “EBV Infection and MS Prevention”.

This report (see below) was the catalyst for creating the Preventive Neurology Unit (PNU), which is embedded in the Wolfson Institute of Preventive Medicine. The funding for the PNU allowed us to employ Dr Ruth Dobson to be the academic lead on the MS Prevention workstream in the PNU. All we need now is a sterilising vaccine against EBV, the necessary funding so that we can set-up an international anti-EBV MS Prevention study and support from the public to do this study. Once we have all these in place we will be a position to finally test the hypothesis that EBV is the cause of MS. There is nothing in the field of MS research that excites me more than testing this hypothesis. Do agree? What excites you? Any other recommendations?

CoI: multiple

91 thoughts on “What is the most exciting MS research on the horizon?”

  1. Any comments on Moderna’s mRNA EBV vax in development?

    Thoughts on if there is molecular mimicry at play, could a vax induce a similar response? Is it possible for one to engineer an ab response to avoid that potential?

    Godspeed on your recovery!

    1. EBV may still be driving established MS, which is why we are working on EBV in MS in general and want to test antivirals in MS.

      1. “EBV may still be driving established MS, which is why we are working on EBV in MS in general and want to test antivirals in MS.”

        At least a little hopeful for someone like me with PPMS.

  2. what do you think of the neuralink ? do you think it will help people with ms ?

    what do you think of the Hadassah stem cell treatment ? does it not look promising for people that are already affected by ms ? i think its great aiming to stop further people from suffering but what about the ones that already are ?

    1. RE: “… stem cell treatment …”

      What is the hypothesis being tested? If it is HSCT to cure MS, then yes. If it is mesenchymal stems cells to modulate the immune system or to repair the damaged CNS I am less enthusiastic. Modulating an immune system is complex when you don’t know what is the primary or secondary abnormality to whatever is causing MS. Repairing a damaged nervous system is very complex; it is not just about cells, but regrowing scaffolding, removing gliotic scars, rewiring, inhibiting inhibitors of remyelination, promoting plasticity, synaptogenesis, rehab, etc.

      1. As I remember there was a Channel 4 programme a little while back, following the well-known UK lawyer Mark Lewis as he underwent this (much hyped) treatment in Israel.
        Sadly, for him it was a failure.
        Personally, I’m extremely dubious.

      2. thanks for replying 🙂

        do you think it failed ? he didnt get further treatment if we could have it every six months to sustain improvement could that not be treated as an add on feature of treatment after hsct or along side a monthly dmt ?

      3. Yes, I do think it failed and I am also deeply sceptical about this strategy.

      4. PwMS should only participate in trials of MSCT and not pay anything for this participation. When you are asked to pay for trial participation be careful. This would be considered fraud in the UK and would not get ethical approval.

      5. Do nothing and it works for some, this is why you do proper controlled trials

      6. Sorry Prof – should i read this as ‘yes’ you are positive of the HSCT to cure MS hypothesis?

        Like Sid, i was also excited by the title of this post. However, research and practice are obviously too different things and as MD pointed out the other day, the prospect of an EBV vaccine could still be some 10+ years away, by which time many ships will have sailed off into the horizon. Can i ask what most excites you on the treatment horizon as this is what patients are most concerned with? thank you

      7. Re: “..‘yes’ you are positive of the HSCT to cure MS hypothesis?”

        Yes, I think HSCT and alemtuzumab may offer some pwMS a potential cure. The problem we have in the field is defining and confirming a cure. What does it look like?

      8. This post just reignited. I thought it had burnt out. I’m not sure what a cure would look like, not thinking about MS every waking hour would be part of it though and one of the reasons I am considering HSCT being on a highly effective treatment (Ocrevus) and relatively early in my diseases course. Thanks for the reply Prof. Another notch in the ‘reasons for’ column for a trip to Moscow

      9. Prof G. your expert opinion is requested:
        Let’s assume in 10 to 15 years (or ASAP) disability progression due to MS related (CNS compartmentalized) neuroinflammation and neurodegeneration can be fully halted.
        What would the next generation of curative medical interventions be to improve or even restore lost neurological function in Advanced MS reversing accumulated disability?
        What do you think that must be done to enable future treatment of Advanced (progressive) MS?
        #thinkbig #thinkdifferent #imagination #determination #moonshot #beyondremyelination #letsstart2cure #advancedmultiplesclerosis

      10. Re: “What would the next generation of curative medical interventions be to improve or even restore lost neurological function in Advanced MS reversing accumulated disability?”

        I sandwich or cocktail of treatments in combination with anti-ageing strategies. I have posted on this many times on this blog.

      1. The fact they’ve put a video on YOUTube should tell you something.
        I’m going to be diplomatic and say no more.

      2. i thought aaron boster was quiet a well respected neurologist ? he works on YOUtube i suppose there is snobbery in every walk of life 😉

      3. I was referring to the YouTube link you posted referring to the Hadassah centre. I have no particular axe to grind with Aaron Boster.

  3. Can definitely see that this is exciting and important. However, as someone with MS even more exciting would be a cure. Can but dream, I suppose.

    1. Re: “…as someone with MS even more exciting would be a cure..”

      We may have achieved this already, albeit in a very small number of patients. The problem is convincing the MS community what an MS cure looks like.

      1. “The problem is convincing the MS community what an MS cure looks like.”

        As a person with MS for c.15 years, I can see that defining what a cure looks like is more complicated than for a disease such as a blood cancer. For those who have had MS for a while a “cure” is to stop any more progression / worsening. I’m not expecting to run again ie I doubt I’ll see a reversal of existing damage, but I’d like to wake up in the morning knowing that I’m not getting worse and I’ll be no worse in 1 year, 3 years, 5 years. Psychologically this would be a huge win for people with established disease – it would provide added impetus to a healthy living / exercise regime.

        On prevention (as a cure to protect those from getting the disease) I would hope to see the equivalent of the human papilloma virus (HPV) vaccine (which my daughter had). This is to reduce the risk of cervical cancer (and some other cancers). A similar approach for ebv should reduce the risk of getting ebv diseases (such as MS).

        For many, a cure means reversal of all damage caused by MS. I can’t see this happening in the near future. The best chance is for those where the disease is at an early stage and where treatments can amplify natural repair processes. Too many research teams have made big claims about treatments to “roll back the ravages of MS…..” I’ve lost count of the fund raising efforts of MS societies promising remyelination or repair of lost brain cells using stem cells etc. We need to be honest – partial recovery of lost function is the most likely outcome.

  4. “an international anti-EBV MS Prevention study” – is it really that exciting? The horizon, I would guess, is 15-20 years time (for an anti ebv drug to be prescribed to those at risk of developing MS). So most of us who follow the blog (and probably our children) won’t benefit.

    When I saw the title of the post I did get excited. I thought you were going to highlight some research that might deliver something beneficial in the near future for people living with MS today – something to tackle smouldering MS, something to promote some repair etc.

    EBV as a possible cause of MS was mentioned to my friend (who developed Bells Palsy) when I attended a neuro appointment with her in c.1985 – she’d mentioned to the neuro that she had a bad case of glandular fever a couple of years before. Even by MS research standards, the pace has been slow.

    You also underplay the resistance of some of your colleagues and pharma. The colleagues will look red faced after 30 years of producing papers on EAE and pharma will loose tens of £ billions of revenue if an ebv vaccine replaces their expensive drugs.

    On a positive note, I’m glad to see you back and enthused. Too many Covid 19 posts of late and I fear we will see 2 more years of MS / Covid 19 research / papers which will dominate MS research conferences to the detriment of real MS research.

    Keep up the recovery effort.

    1. Re: “Too many Covid 19 posts of late and I fear we will see 2 more years of MS / Covid 19 research / papers which will dominate MS research conferences to the detriment of real MS research.”

      I agree. I am Zoomed and Covided out as are most of us. All I want is to be able to go for a jog in the sunshine and to get back to focusing on the core issues of MS research; MS prevention, targeting smouldering MS and curing MS.

      1. I haven’t got time to wait for an anti-EBV drug to come to market for MS patients. You’ve always promoted self-management, so I’m taking responsibility for my own treatment by:

        1. Hanging around gay bars (don’t tell my wife) with the aim of getting onto HAART treatment;
        2. Eating 12 doughnuts each day so I develop Type 2 diabetes and can get on Metformin.

        My hope is that HAART will deal with the underlying cause of MS and Metformin will promote some remyelination.

        I will of course continue with my Vit D supplements and Alpha Lipoic Acid supplements.

        It’s a pity I will have to go to these extreme measures, but I’m guessing you’re not interested in starting a small trial of 10 patients on a combo of HAART and Metformin to see how they do over 5 years? The trial could be funded by sacking the Mouse Doctors, the savings on mice food, selling half of the bottles in your wine cellar.

      2. Well, you’ve (partially at any rate) got your wish.
        Hope that cheers you up.

    2. for once i have to agree! my ms started after my partner had glandular fever which i probably also had! it was around a month after she started feeling ill that my legs went numb! however we had both just recovered from covid so the glandular fever was overlooked. i truly believe the ebv kicked my ms off im also progressing and feeling rough as hell and my gp is going to do an anti body test for ebv i think purely out of interest he has.

      1. That seems a very quick turn around from glandular fever to MS. My feelings are it takes much much longer. But what do I know…

      2. Yes, the only time (s) I can recall being ill with anything that might have been EBV were in my teens, long before MS diagnosis. But I don’t know anything either 🙂

      3. An MS outbreak study in school children in Denmark suggests the time from infectious mono or primary EBV infection to MS could be as little as 2 years.

      4. As a teen I had endless swollen glands and a few bouts of severe flu like illness but no-one ever mentioned EBV, which I suppose it could have been. But if it was and led to MS the transition took decades to be noticeable. Interested to know why the majority of those who know they had EBV don’t get MS if that’s what is driving it?

      5. It’s a conundrum, EBV infection is very common (at least 95% of people are infected), yet a likely 100% of pwMS are EBV positive. So, EBV isn’t the sole cause and there are other factors involved such as genetic background, vitamin D etc but it is an important driver.

      6. Hey all just incase anyone was interested, i got my blood work back from my gp and i have no evidence of EBV no active infection or anti bodies! So do i still have ms caused by EBV ? how would that work ?

      7. Pakpoor et al. The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis. Mult Scler. 2013 Feb;19(2):162-6.

        Background: Epstein-Barr virus (EBV) infection is widely considered to be a risk factor for multiple sclerosis (MS). A previous meta-analysis estimated an odds ratio (OR) for MS in individuals seronegative for EBV of 0.06. Given the potential importance of this finding, we aimed to establish a more precise OR for adult and paediatric onset MS in EBV seronegative individuals.

        Methods: PubMed and EMBASE searches were undertaken to identify studies investigating the association between MS and EBV. Twenty-two adult and three paediatric studies were included. ORs were calculated using a fixed effects model. A sub-group analysis based on the method of EBV detection was performed.

        Results: The OR for developing adult MS in EBV seronegatives was 0.18 (95% confidence interval (CI) 0.13-0.26)) and for paediatric MS was 0.18 (95% CI 0.11-0.30). Sub-group analysis on EBV detection method showed that studies which used immunofluoresence generated an OR=0.07 (95% CI 0.03-0.16); for those that used enzyme-linked immunosorbent assay (ELISA) OR=0.33 (95% CI 0.22-0.50) and for studies which used ELISA and immunofluoresence OR=0.00 (95% CI 0-0.43).

        Conclusion: The sensitivity and specificity of the assay used to measure EBV antibody titres have an influence on the association between MS and EBV. Looking at studies where two independent methods are used and therefore are likely to be the most robust, EBV appears to be present in 100% of MS patients. This has implications for future studies of EBV in MS. MS patients without EBV infection, if they truly exist, should be studied in more detail.

  5. I agree 💯. I progressed (worsened) over the period of a year 2018-2019. I was never sick. I slowed down, balance disappeared. “MS” fatigue. No infections and it was determined to be progression.

    A brilliant gp sent me for a whack of tests and surprise – I had active (and historical) Epstein Barr virus. I was not sick. No fever, swollen glands. I felt fine. My immune system was tied up fighting this thing and I wasn’t able to get rid of it for good.

    I realize fully that most of the EBV talk is about causation, but I believe the dialogue can be opened up to progression.

    I was put on antivirals and within a few weeks, most of my mobility returned. I was able to catch a cold and have symptoms of my immune system fighting it.

    I stayed on antivirals through the first part of year 1 Mavenclad. A little tired again once I dropped the antiviral and my immune system hit normal but nothing like before.

    I suspect that an EBV vaccine would have been just as helpful.

    I’m not saying that this will be every person’s experience. But I’m so grateful a gp thought outside the box on my behalf.

    Year 2 this month.

      1. A full EBV panel, testing viral capsule antigen (VCA), early antigen (EA) and EBV nuclear antigen (EBNA). Interpretation is complex.

        I was put on acyclovir which is not supposed to be good for it but did help me. I have friends who have had some success with valacyclovir. Antivirals don’t solve the problem. They limit viral reproduction – for me, it felt like my immune system could get back to doing what it was supposed to. Closer anyway lol.

        My biggest concern: I see trials with combos of metformin, fungicides etc. They may work beautifully for some but not if one’s EBV status is the driving force. Likewise, an EBV treatment may be preventative for MS, but won’t do much for one with MS if something else like a chronical subclinical fungal infection is driving progression.

        It’s a conundrum.

      2. thanks for sharing your acyclovir-experience – a lot of us get stuck with the ‘there’s no anti-viral for EBV’ and just have to sit it out, even if it takes a year… Having something that takes the edge off, must be a relief

  6. This prompts a question I’ve been struggling with for some time now. I’ve had several reactivations of EBV (one co-inciding with starting interferons (leukopenic), one whilst on DMF (lymphopenic)). The effects were really debilitating, the first time for ‘only’ 4 months, the second time for over a year (barely able to walk, losing my job, etc.). In my experience, EBV-reactivations have had a far worse impact on my quality of life than MS. For fear of another EBV-reactivation, I quit DMF about 7 months ago. I have been looking into first-line DMTs that would possibly work against MS and EBV, and I’ve come up with glatiramer (https://nn.neurology.org/content/7/6/e876) and teriflunomide (https://pubmed.ncbi.nlm.nih.gov/31525628/). I would be very grateful for any comments on that, or references for further reading…

    1. I wanted a B-cell treatment. My hypothesis well before finding Bart’s Blog was that EBV is stored in memory B cells, and I hoped to get on a treatment that would do some damage to those cells. Hopefully regrow new naive B cells that would have a clue.

      Year 1 Mavenclad completely removed my fatigue, especially cognitive fatigue. I don’t know this is the reason of course. But it’s my hypothesis.

      I agree that EBV reactivations do a ton of damage. Mine aren’t even obviously EBV. I just get slowly worse. In my case, it’s disabling … and called MS. Perhaps MS is the reason these chronic conditions contribute to “worsening” or “progression” – but we need doctors willing to look deep rather than sweeping all declines under the MS rug.

      1. I agree – it’s not only the interaction between MS and EBV that is important, but also disentangling (to some extent) MS and EBV by medical practitioners

    2. Re: “EBV-reactivations have had a far worse impact on my quality of life than MS”

      How were these diagnosed? Viral shedding in saliva?

      1. no, as KC notes, having MS makes diagnosis of EBV a lot harder, since it’s not the first (or second) thing that comes to mind when sudden symptoms emerge. Eventually, EBV was diagnosed with serologic tests (VCA, EBNA).

      2. Prof G, could I ask what your thoughts are on EBV-specific CD8+ T cell production by glatiramer acetate and possible anti-EBV effect of teriflunomide?

  7. The keto diet and intermittent fast study in Germany, hopefully the results are published soon. Anything lifestyle based is exiting as it put abit of power into the individuals hands.

    Gold Nano crystals are pretty exiting

    There seams to be a reluctance towards anti EBV trials or antiretroviral trials in MS considering the evidence of EBV inhibitors and people on antiretroviral treatment for other diseases doing well and reducing there MS symptoms, there’s a massive clue there and it looks suspicious why there wouldn’t be trials.

    Hope fully potential Moderna and Atara treatments towards EBV show promise but seams so slow.

  8. EBV theory is really something that should be tested in people with MS. I hope you will succeed putting together a clinical trial for that. As it takes time and time is brain, I am just wondering if there is something easily accessible until then that can be tried in progressive MS by physicians off-label. What do you think of a combination of lipoic acid (neuroprotection) with N-acetylglucosamine (remyelination)? Can they work together? No offsetting interaction? Both seem safe and can be bought easily. Looking forward to your opinion.

    1. If you really are committed to the EBV hypothesis as a foundation and rationale for an EBV vaccination programme, you, your team or someone else will have to show the mechanism by which the pathological events observed in the MS lesions are specifically driven by the EB virus. Despite a very large literature attempting to do this we still cannot link the tissue MS events to either the presence or activation of the virus.
      The molecular tools are available to pin down the pathological mechanisms that can account for MS. Its just a serious intention to use them that’s lacking.

      1. “The molecular tools are available to pin down the pathological mechanisms that can account for MS. Its just a serious intention to use them that’s lacking.”

        Whatever these “molecular tools” might be, I think to suggest that the MS research community lacks a serious intention to use whatever is available is very well wide of the mark.

      2. cannot link the tissue MS events to either the presence or activation of the virus….You dont need to do this to have a working hypothesis involving EBV

      3. Re: “….pathological events observed in the MS lesions are specifically driven by the EB virus.”

        EBV may simply be the essential trigger for autoimmunity; EBV transactivates HERVs which stimulate PAMPs and they lower the threshold for B-cell activation. It doesn’t have to be direct EBV infection of the brain.

      4. How many times have I read on this blog by (GG) that he does not believe that MS is ‘autoimmune’. If EBV can be shown, in any context to activate CNS autoimmunity, the difficulty, to which you very frequently refer, in getting support for further EBV?MS research could be somewhat less of a problem!

      5. I would advise you to prepare for a trip down the EBV/Memory B cell rabbit hole 😉

  9. I was diagnosed with glandular fever at 16 and again 25 years later. It would not surprise me to hear that this was the cause of my MS. I would like to think that there will be a vaccine to prevent glandular fever.

  10. I desperately want to get a handle on the causes of the higher incidence of depression in pwMS. I asked about this at the point of diagnosis. Neurologists both sides of the channel assured me that any depression I had experienced was not associated with having MS. They were both eminent neuros from two centres of excellence, but they didn’t provide me with a reason for their answers. Subsequently I continued to be visited by the black dog and the whole package seemed chronologically linked. I had it around the time I first had MS symptoms. I need answers.

    1. Depression and MS could be linked by cytokines with high levels present in MS maybe. There are links between depression and inflammation so that could be a link.

      Also a diagnosis of MS doesn’t put anyone in good spirits also triggering anxiety and not knowing what could happen in the future.

      All linked

      1. Thanks for the heads up re: cytokines. A cytokine storm might be a culprit in MS, whereas the trigger in the gen. pop. might potentially be from other causes. For myself, I seem not to have that gene that processes things like this, as I was completely unconcerned when I got the diagnosis. It could be concerned with my strange premonition when an SRN trainee on my way to my shifts at the Royal South Hants, when my bus passed a famous MS billboard depicting a woman with part of the image missing – her spine. I thought “I’ll probably get that.” Even more bizarrely, two months later, I caught glandular fever…And I never returned to nursing.

    2. Depression and anxiety are interrelated and complex disorders. Social circumstance, cognitive biases, locus of control, and physical health all play a role. I suspect pwMS exhibit significantly higher levels of health anxiety than the average person given the variable nature of the disease and risks associated with treatment. Anxiety and the associated stress response can result in depression. I also suspect many physicians do not want to facilitate this health anxiety by ascribing all health related issues to MS. With that said, MS damages the brain and it seems reasonable that this damage may result in depression. The temporary relationship you outline also suggests MS may be a causal factor. You know your body better than anyone. Talk to your neurologist about available treatments. Many don’t involve medications (e.g. CBT, DBT, exercise etc). Finally, be kind to yourself. Acceptance without reason can be therapeutic (I don’t have MS but know the Black Dog very well).

  11. Let’s say an EBV vaccine is developed and over time, results in a reduction in the incidence of MS. How would this benefit people who are currently living with the disease? What are the potential cascade of treatments that could follow?

    1. Re: “How would this benefit people who are currently living with the disease?”

      Possibly reduced anxiety about their children, siblings or other family members developing MS. I am aware that some pwMS decide not to have children because of anxiety about their children developing MS; knowing that MS is preventable may allow them to reconsider their decision.

      1. Seriously? Is that it? I never wanted kids anyway, regardless of my PPMS. Are you saying that someone like me need not bother following EBV research?

  12. All linked to gut health somewhere down the line. The faster the gut microbiome is understood the better for everyone’s health.

      1. I am, it’s an untapped powerhouse right inside our body, it shame we don’t fully understand it.

        Wise to look after it

      2. EBV could be considered to be a part of our metagenome and part of our microbiome. I have little doubt that with CMV and other herpes viruses EBV shapes and sculpts or immune system in many ways.

  13. Several powerful comments about EBV and the benefits of antivirals.
    Like many others I had a severe bout of glandular fever as an adolescent.
    On the occasions my sister, who has Sarcoidosis, has been tested she’s full of EBV, despite no obvious symptoms.
    QUESTION: should we be flagging this up with our GPs and discussing with them whether they’d be ok with routinely testing OR with routinely supplying antivirals?

    1. Even my neurologist won’t speak to my EBV issues. Although hopefully she is noting that I was able to stop antivirals after Mavenclad year 1 month 7 – first time off since 2018. No crash.

      Yes, our primary care physicians need education for sure, not just in an EBV, or CMV or other viral sense. There are so many restrictions on antibiotics (as an example) … hitting a wheelchair because your UTI is subclinical and you are refused treatment should not happen. But it does ALL.THE.TIME.

  14. Or disentangling other things.

    We seem to respond neurologically, rather than with typical symptoms (in my experience) to subclinical infections of any type.

    Convincing a doctor that you need treatment for a bacterial infection without presenting fever or with a bacterial count of “less than cutoff” is impossibly difficult.

    Could an immune system be so tied up fighting to keep things partly controlled, that it sucks away neurological reserve leaving one with ms symptoms only? Resulting in “it’s just progression”.

    I have friends in similar situations to me who (with great doctors) have found CMV, well established fungal infections (especially if on immune suppressants), etc.

    So with respect to established MS, it’s having a super-hero clinician willing to disentangle many pieces when there is evidence of what looks like progression, when it is in fact worsening due to “x, y, z”. When x, y, z are often manageable.

    At this “progression” end, I don’t believe it’s just EBV. That has been my situation. The issue is us having neuro decline as the only symptom of many things that aren’t investigated fully.

    Because – “just MS”.

    1. I know post finding out you have MS. I’m 36 not married, drs won’t let me drive anymore, I know it’s a whole other monster, I just want to know how the monster got in! EBV does make it make sense.

  15. As far as I know, it might not be EBV as the viral trigger, but I have been tested and resulted positive for EBV IgM antibodies in 2006 and then triple the normal high value in 2008 and again in 2016. I know it’s why my MS is aggressive, but can’t find any treatment for the chronic fatigue, elevated body temperatures, or excessive immunoglobulins. I have also had shingles a few times, though I blame the high dose cyclophosphamide clinical trial I went through in 2004 to my immune system oddities.

  16. Could there be MS research on the following?….

    1) Spironolactane and MS, as this heart failure drug inhibits EBV.

    2) Dipyridamole and MS, as this drug prevents EBV reactivation.

    3) Vitamin C and MS, as low vitamin C is often found at time of EBV infection.

    1. Are there any pwMS who take Spironolactane for heart failure, and have noticed less progression in their MS or a reduction in their MS relapses?

      1. MD thanks. I’ve been reading into it as unable to sleep. Of the few studies of MS and vitamin C that have been done, MS patients during relapses show a significant reduction in vitamin C levels, even though the intake of vitamin C is not reduced or lower than the general population.
        And also read that vitamin C is required for formation of the myelin sheath.

      1. When I suggested to the Specialist who confirmed my MS that being twice diagnosed with glandular fever (25 yr interval) might be the cause, he denied it. I have also had Shingles as well as Measles, Rubella, Mumps and Chicken pox as a child as there were no vaccines for these ailments when I was growing up.

  17. I had mono three times in HS. I was a really good tennis player, decided I couldn’t play my senior year. I was falling at 17, finally diagnosed with MS at 34. I always ask people’s I meet with MS if they had Mono. Pretty good study to complete!!!

Leave a Reply