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  • Can I ask a question about disease onset please. I posted this before but the thread was quickly overtaken. Using the McDonald criteria (space and time) it is difficult to receive a diagnosis until a second event has occured. So if a CIS case converts to MS in say 5 years, you may be treated within 6 months of the diagnosis but this is still 5.5 years after the onset of disease, is it not? So whereas a large gap after the initial episode is considered a positive prognostic factor, this is countered by not receiving or being eligible for treatment during the initial, critical period. Is this not a major flaw of the diagnostic process?

    • It can happen with one event if the scans show the time and space and if you ntice the recent licences of cladribine, ozanimod, siponimod go from CIS to active SPMS

  • If it is seen that when used early lemtrada can halt ms progression and in theory could be made safe if followed with b cell depletion ( ocrevus rituximab) and mavenclad has been found to remove O bands in csf then why are we not using a combination treatment from diagnosis ? ie. 2 years of lem followed my six montlhy doses of ocrevus followed by two years of mavenclad ?

    • Ask youself why do you have write in such a tone…. Do you want me to respond in a similar one?

      De Silvestri describes the composition and dosing of the combination therapy, which contains the antibiotic minocycline, the anti-fungal agent fluconazole, and the cholesterol-lowering medication atorvastatin. ProfG did the rounds about interest in a polypill a few years ago, there was little interest, so we can come back in 5-10 years and see where this.

      But reading the patent it says “These MS subjects showed significant functional recovery as early as the first week of administration, through 45 days”…sounds like the biotin effect and we know what happened there. To have an effect so quick would imply repair

      • Not commenting on the tone, but on the content.

        I find it quite interesting that bacterial and fungal causes also always pop up once in a while (besides EBV/herpes).

        I’d love to finally see a study combining ALL of those different findings on bacterial, fungal and viral infections. Everybody always seems to just look at parts of the whole picture. Somehow all researchers in relevant positions (with fundings) seem to have blinders on and not being able to believe that this disease might be caused by different pathogens.

        This “miracle formula” also misses a vital point in the pathogenesis of MS with anti-virals missing from it.

        • I agree x 100. I take an antiviral to function with MS. Not a great one but it’s the difference between function and non-function.

          Either add an antiviral to the cocktail drug to cover all eventualities, OR I wish practitioners could take the time to evaluate what exactly a person with MS IS fighting and treat accordingly.

          Problem is – we get no symptoms of the “thing” – just MS worsening. Which is confused with progression.

        • HSCT uses large doses of antibiotics, antivirals and (probably) antifungals while your immune system is rebuilding. Maybe that’s part of the MoA?

          • As far as I know there’s not a single MS related study combining antivirals, antibiotics and antifungals, which is a shame, since there are plenty of findings indicating involvement of different infections.

        • I agree. I have multiple immune deficiency problems, (such as impetigo that doesn’t heal, etc.). I would like a doctor to invite all the different consultants to have an overview of my various ‘complaints’ and make a team decision with me about how best to support me medically. I think this may be financially nonviable, but it would be good to bring all the experts together with the person who is an expert in how her own body does or doesn’t function well.

    • I had thoughts on this in October 2019 but now have more…It is all T cells when you read the paper. I ask you to apply the Smack you in the eye test and ask what you think, I will put them there for you to comment

  • Still hoping to find out which treatment for rheumatoid arthritis ProfG was comparing immunosuppressant treatments with when discussing the increased longterm cancer risk among MS patients.

    The point was that the RA drug has been around since the 80´s and had similar depletion effects however an insignificant increased rate of malignancies.

    Maybe ProfG is around and reading this time to give a name.


    • Maybe rituximab? I think in the 80s and stuff we had mainly non-biolgic DMARDS for RA – small synthetic molecules – still used to this day. MTX is cheap and good for moderate to more severe RA. I think biologics in RA started being used from the late 90s. We don’t fully understand the cancer risk long term because people haven’t really been taking these biologics long enough. A bit like all these new novel treatments for MS. Patient pioneers in a way.

  • The results of the Phase 2 Bexarotene trial (from the brilliant Cambridge research team) are being presented at ACTRIMS / ECTRIMS 2020 on 26 September 2020. The title of the presentation is:

    LB01.02 – Phase 2 clinical trial evidence that a retinoid-X receptor agonist promotes remyelination in people with relapsing-remitting multiple sclerosis

    Seems quite a positive title for a presentation or am I reading too much into it?

    • SID
      Looks that way but We will have to see when the abstract becomes visible…lets hope, but don’t you have a hotline to the brilliant team so you can tell us how well its worked. It is in the late breaking session however we did have MS-SMART as a late breaking session, full of hope and then dashed.

      However one wonders if the results are so good, why the next trial with metformin and clematine

      • Fingers crossed.

        I’m not saying that Team G are not brilliant. It just seems that you have been stuck in the Covid 19 swamp for a bit. Covid 19 will pass, MS will remain. We need to move forward the trials which address the real MS.

  • Since the Oxford vaccine seems to be amongst the front runners, can anyone confirm if someone who is immunosuppressed can have it? It is a chimpanzee adenovirus vector, but modified so that it can’t reproduce after the initial infection of cells causing them to produce the spike protein and leading them to generate an immune response to it. My thinking is that if it can’t reproduce after initial infection then the answer to my question is yes, but just wanted to check what other people are thinking.

    • I believe it a live vaccine and therefore may be contra-indicated in immunosuppressed people I appreciate that it is replication incompetent but I guess it will need to be trialled

  • I started on a clinical trial here in Berlin a couple of weeks ago. It was a day full of tests which will be repeated annually for the next 10 years. As this was just to set the baseline, I wasn’t told much about what they found out other than that the messages between my eyes and brain were taking longer than they should be (VEP). Other than that my eye pressure, sight and peripheral vision all tested normal. I know I should have asked more while I was there, but I was a bit overwhelmed by it all and now I have to wait until my next neuro appointment in October to find out more. Could you tell me what the effect of the slow-moving messages could be on my sight? I haven’t noticed anything other than that I need reading glasses now – but the optician said that’s because I’m old. Thank you!

    • Slow moving mesages may suggest some demyleination in the optic nerve but the influence may be dependent on where the demyelination is. Much of your vision focuses to certain points of the retina, if the nerves innerate a different part of the retina, you may not notice the effect too much

  • Is there an optimum time during Mavenclad treatment to have vaccinations? Specifically wondering about an eventual Covid vaccine, but also flu. I realize I will be waiting for a non-live vaccine.

    Would someone base vaxx time on lymphocyte level or time after treatment weeks each year?

    Thank you!

  • What would be the implications for someone on Mavenclad who only finishes 3 weeks out of the total of 4 over the 2 year treatment period because of low lymphocytes that don’t recover enough for the final week of treatment? All the trial work done on the medication and sustained efficacy has looked at the standard treatment protocol and I’m just not sure, even if it is even possible? Would it just be reasonable to assume that it may be less effective?

    • This situation won’t arise because we don’t check blood counts between cycle 3 and cycle 4 of course 2 of oral cladribine. The nadir of the lymphocyte count occurs 2 months after the last cycle. Contrary to what people think the depletion kinetics of lymphocytes are relatively slow post-cladribine and occurs over weeks to months. This is, in my opinion, an advantage of cladribine,

    • In the trial they ploughed on with the dosing without checking for repopulation but it is not dosed to lymphocyte nubers if you havent repopulated you dont get more doses, I suspect that 3 out of 4 isn’t going to make a huge difference

  • I had read a comment about Ocrevus treatment and that once started, you should not stop after 2 or 3 infusions as you could develop anti drug antibodies and therefore not subsequently be able to resume it (effectively) later. If, as an Ocrevus user, you were to seek an alternative IRT treatment such as lemtrada or HSCT, does this prevent a return to Ocrevus later?

    • I have a suspicion that HSCt would probably wipe away those ADA (if you get them in the first place) but it is an interesting question for sure

      I think the Russian protocol actually uses rituximab as a final step to deplete any remaining cd20 cells so go figure.

    • I’m guessing the first thing to think about is why the switch to another IRT?
      I was due an additional 3rd dose of Lemtrada in January due to new lesions on MRI. Covid happened which took that off the table so I started Ocrevus with the understanding that I could go back to Lemtrada if needed. I didn’t develop Lemtrada antibodies so it’s still (at least was) an option. If I had developed antibodies this would be a definite no. I assume this would be the same the other way round.

      • I didn’t develop Lemtrada antibodies so it’s still (at least was) an option

        Was this offered, if they ar enow being measured thats good. P.S.it is rather odd you didnt as about 85% do make them

        • I’m a RLH pt so was checked to establish whether it’d be worth 3rd round. This might mean something? Round 2 was 2017. MRI lesions 2019. Haven’t developed any autoimmune issues. No thyroid issues, no shingles……… I didn’t even get the dreaded infusion rash! Just s tiny bit of what looked like prickly heat. Side note: Think I may have been first to have 2nd round sub cut. Steroids and I are not friends……..

          • Thanks, I think most of people at RLH will get checked now and I certainly doubt anyone will get a third round without this being looked at, at two years after last infusion enough time for any ADA to disappear.

    • This is a hypothesis and not supported by data there is a literature on switching. If you have anti-drug antibodies it could have an effect but with a single infusion, it will have had its effect before the ADA become a problem…probably

  • Thank you so much!

    It’s doubtful a non-live vaccine will show up prior to January so guess some of us will be well quarantined again lol

  • One of the topics at Joint Actrims/Ectrims is the following

    Radiological advances and machine learning approaches and how these techniques can help us better understand MS

    About time Barts jumped on the bandwagon?

  • Could autologous stem cells, destined to be T cells, be harvested, genetically modified to express anti-EBV factors (like AdE1-LMPpoly) and then grafted back into the host to kill EBV infected B cells in perpetuity?
    As we can make two kinds of HHV3 vaccine, why hasn’t anybody successfully made an HHV4 vaccine yet?

        • I think mostly we have seen ATA188 which is not all that impressive but also not autologous. ATA190 (the autologous one) is missing any study with a reasonable sample.

          From what little I have read about CAR-T in cancer, it *can* work spectacularly well but the risks are still high. Not to mention the pricing.

          • The autologous one is too specific for the individual to be a commercial product and the allogenic one to me makes no biological sense.

            CAR-T could be great but until you can get rid of them after they have done their job, it is a disater waiting to happen

          • The situation with cancer is obviously a bit different (short term mortality increasing willingness to pay) but I am not sure you could not profitably marketautologous treatment for MS – if it really leads to long term remission (proving that will be the major issue I think).

            6 figure HSCT treatments are being done, after all.

    • That is the basis for a new investigation. ATA188. Atara biotherapeutics. Using t-cells from healthy donors that are modified to destroy EBV infected b cells.

      I WISH. I would be first in line for that vaccine.

  • What is the drug should be created to stop MS from progressing beyond the damages it already caused? I mean stop additional new damages from occurring, not those that are already set to occur.

    Today many posts were done but the email links point to older posts. The post about twins and the one about the b cells expanded in the brain. The latter points to a similar work presented at AAN2020 and both works tell more or less the same thing between the lines: get rid of antibodies and antibodies-making cells. So, I cannot avoid to ask this question like a kid would do: when will sizomus trial start? My expectations are high for it.

    As usual, thank you for the information and in particular for the monthly Q&A post. I find it a great way of connecting people and thoughts.

    • Every no an again I have a brain fart and posts get published before they are ready to be publish, I think the twins and B cells were launched by mistake however they have been finished now. THe twins paper was just published last week, but it was submitted last year as a pre-print. I reported on the paper at that point.

      AAN2020 did not happen so all we have are the abstracts…some of these have moved to ECTRIMS 2020.

      Sizomus is ready to go…covid delayed the start

  • Thoughts on having a lumbar puncture to check for disease progression due to a big change in symptoms several years after original diagnosis; MRI’s somewhat stable. Mainly changes to the C & T Spine. Been reading biomarker studies of the spinal fluid giving clearer picture & helping figure out treatment course. Most MS people think lumbar punctures are “one & done” for diagnosis only.

    • This is what the neurofilament boys and girls form the USA want as they dont like lumbar punctures thereofre serum neurofilament is being pushed…I am not sure it is good enough

  • First off, love the Chihuly glass sculpture MD.

    Question: Say someone had a EBV Vca AB Panel performed at the time of confirmed MS diagnosis, yet before starting a DMT. Then say this person, used an anti-CD20 as a first line treatment (3-4 cycles), and subsequently began using a some what lower efficacy DMT (with antiviral aspects) during the time of circulating b-cell reconstitution. Would retesting the EBV panel show any changes from the baseline results taken pre-DMT?

    Not sure it’s even a relevant question; however, there seems to be some recent discussion around losing vaccination responses, so that got me thinking, what about prior exposure to certain viruses.

    • Well spotted…many were especially commisioned for Kew Gardens…Maybe I will do some more for Q & A.,,,
      In answer to your question I dont know, but one you are infected with EBV youve got it and may not be the same as occasional infection as encountering the infective agent consolidiates your immunity

    • somewhat on a similar note: I had an EBV-infection at a time when I was using interferons. I switched to DMF (lymphopenic for 3 years straight), then got EBV again. This time it lasted much longer and clinical symptoms were much worse.

      • I have struggled with chronic reactivating EBV since 2013. Thankfully started Mavenclad early 2019. It has fast B memory cell depletion, and my naive B cells seem to be behaving themselves.

        I’m down to a half dose or the (not terribly effective) antiviral I’ve been on since 2018, and feel GOOD!

  • Thoughts on lumbar puncture years after original dx to help determine rapid disease progression. MRIs are not giving enough information. Seen several articles/studies on helpful bio-markers from spinal fluid they can assist in telling if current DMT is helping, disease is active but MRI aren’t enhancing etc.

  • If the COVID-19 vaccine is a live vaccine, what precautions would someone on Ocrevus need to take it their family (partner, young children) have the vaccine? Thanks.

  • I have always been told I need to get a flu shot because the flu can cause a relapse, but nobody is talking (to me) about whether that virus/relapse link is a risk for covid19. I appreciate that you may not KNOW but it seems like something that should at least be discussed. Do you have any insight?

  • Zealot time


    Long-term Follow-Up After Autologous
    Haematopoietic Stem Cell
    Transplantation: The Italian Multiple
    Sclerosis Cohort

    neurological progression is common in multiple
    sclerosis (MS). Autologous haematopoietic stem cells
    transplantation (aHSCT) has been extensively explored as a
    treatment strategy for aggressive MS. However, it’s
    unknown whether aHSCT is able to prevent long-term
    disability progression.
    Aim: To report long-term outcomes of the Italian multicenter
    experience of the use of aHSCT in MS.
    Methods: Retrospective cohort study including aHSCT
    treated MS patients from 1998 to 2019 in Italy, evaluating
    long term (i) 3-months confirmed disability progression; (ii)
    occurrence of relapses; (iii) MRI activity and (iv) treatmentrelated
    mortality (TRM).
    Results: 206 patients were included in the study. Median
    (interquartile range) follow-up was 4 (10-2) years (35 and 7
    patients had at least 10 and 15 years of follow-up
    respectively). 69% of patients were free of confirmed
    neurological progression 10 years after aHSCT. Progressive
    MS patients had a significantly higher risk of EDSS
    progression than relapsing-remitting (RR) MS patients
    (75%vs58%; log-rank p=0.004). 50% of RRMS and 18% of
    progressive MS patients maintained an EDSS improvement
    for 5 years. Over 10 years, 71% of patients were free of
    relapses and 18%. BEAM+ATG based conditioning
    regimen was associated with a reduced risk of relapses
    (24% vs 82%; log rank test p<0.0001) compared with
    Cy+ATG and Thiothepa+Cy based conditioning regimens.
    TRM was 1.5% in the entire cohort [mean time(SD)=41.3
    (25) days after transplant]. No deaths occurred after 2007.
    Conclusion: In most patients, aHSCT is able to prevent
    disability progression for up to 20 years. RRMS patients are
    those who benefit the most from aHSCT.

    Ean 2020

      • https://www.ean.org/congress-2020

        Most of the DMTs for MS do not cross the blood–brain
        barrier (BBB) and therefore their activity is limited to the
        peripheral immune compartment, without affecting CNS
        resident inflammatory cells that are considered to be a main
        driver of demyelination and axonal damage in advanced
        stages of the disease [21]. Data regarding the diffusion of
        cytotoxic drugs across the BBB derive mostly from studies
        in oncological patients. Among the drugs administered
        during conditioning, busulfan showed the best performance
        with a cerebrospinal fluid (CSF)/plasma ratio of 0.95 after
        intravenous administration of high doses [22]. Cy crossed
        the BBB but the ratio was low for active metabolites; however,
        the drug could be activated within the CNS also [23].
        Carmustine has high penetration rates (CSF levels > 50–80%
        of serum levels), while the other drugs in the BEAM regimen
        show rates around 5–22% [24, 25]. It should be noted
        that the drugs’ penetration to the CNS may be affected by
        a pathological increase of BBB permeability, a feature of
        active MS; however, no data are available in this respect.
        No differences in efficacy were detected in the retrospective
        comparisons between BEAM/ATG and Cy/ATG and
        between mini BEAM-like and BCNU/melphalan regimens
        performed in two studies [19, 26], even if the sample size
        was small. Intermediate-intensity regimens are considered
        more effective than low-intensity ones, but no conclusive
        evidence is available yet.

        Haematopoietic Stem Cell Transplantation for Multiple Sclerosis:
        Current Status
        Alice Mariottini1,2 · Eleonora De Matteis1,3 · Paolo A. Muraro1


        You may be interested


        Background: Multiple Sclerosis (MS) is a chronic, immuno-mediated disease of Central Nervous System (CNS), mostly affecting young adults and frequently resulting in a progressive, irreversible disability despite the administration of approved Disease Modifying Treatments (DMTs). Autologous HSCT was shown to induce a high rate of sustained, treatment-free remissions in cases of aggressive MS. Optimal intensity of Conditioning Regimen (CR) in terms of both toxicity and efficacy is still to be clarified. In EBMT Registry the most frequently used CR were BEAM + ATG (BEAM) or HD-Cyclophosphamide + ATG (CYC). Overall TRM was low (1.4%), but slightly higher in BEAM over CYC. Here we retrospectively analyzed the neurological outcome of 603 MS patients who underwent autologous HSCT following either BEAM or CYC regimens.
        Methods: Patient data were extracted from both the EBMT database and a disease-specific database developed by the EBMT Autoimmune Diseases Working Party (ADWP). Patients were selected for having received either BEAM or CYC and the availability of major neurological variables at both baseline and follow-up. MS forms at HSCT were reported as Relapsing-Remitting (RR), Secondary Progressive (SP), Primary Progressive (PP) and Progressive-Relapsing (PR). The impact of variables related to both patients (age, gender, EDSS at HSCT) and MS form at HSCT were also evaluated. Endpoints were failure to maintain a NEDA (Non-Evidence of Disease Activity) status, incidence of clinical relapses and/or progression of disability.
        Results: Number of CYC procedures was higher (331 vs 272, respectively). Gender distribution was similar (p=ns), whilst mean age was higher in CYC patients over BEAM (38.3 vs 36.5, p=0.02). RR forms at baseline were more frequent in CYC group (p=0.004) as well as incidence of Gd-enhancing lesions at baseline (47.2% vs 35.5%, p=0.004). Mean disability at baseline, assessed through the EDSS index, was significantly higher in BEAM over CYC (5.1±1.7 vs 4.8±1.7, p=0.03), with no differences in the number of relapses in the 2 years before HSCT (0.41±0.49 vs 0.39±0.48, p=ns). Analysis of NEDA failures didn’t show any significant differences between the two groups, also when RR and Progressive patients were analyzed separately. Comparison of relapse incidence was also not significant whilst CYC-treated patients showed an advantage over BEAM in progressive patients in terms of both overall disability worsening (p=0.01) and continuous progression after HSCT (p=0.01).
        Conclusions: The non-myeloablative regimen CYC-ATG has become the most common conditioning regimen despite a lack of comparative data with more intense regimens. In our retrospective analysis of the two most frequent conditioning regimens in the EBMT Registry, there was no significant difference in terms of prevention of relapses, whilst the CYC regimen showed a slight advantage over BEAM in Progressive patients in terms of disability progression. The overall low incidence of relapses and the retrospective character of this analysis prevent to draw conclusions in terms of capability of the two conditioning regimens to restore the self-tolerance in MS. A prospective comparative trial is likely needed in order to provide a reliable information for this still unanswered question.
        Disclosure: No disclosures


        Sharing is caring


        • Thanks a lot. I missed the later one.

          Although I do question if the authors understand statistical vs real world significance when I look at the age and EDSS comparison…

          In sum I guess still no clear guidance either way.

  • Hello. (I know, another MS/Covid question). I keep hearing mixed messages, so I’d love to hear the doctor’s opinion on this. I am 41, have RRMS, and am currently on my 6th round of Ocrelizumab (Last infusion was about 3 weeks ago). I also had DCIS with lumpectomy and radiation about 3 years ago. Other than that, I would considered myself pretty healthy (other than the random nerve pain and of course horrid fatigue). We are keeping our children in a virtual school at the moment since I feel that is currently the safest for us. My husband wants to see his family (including siblings), which I completely understand, but his brother has his children going to in-person school. These kids also see his folks almost everyday. (Added info: His folks most likely had COVID-19 when this pandemic started and got over it.) Would this unravel the fact that we are keeping ours out of school? And would you figure the risk is too high to see his family? He is not too happy about not seeing his family, which I don’t blame him. I just don’t know if the risk is too great or if we most likely would be fine…there is so much mixed information I get. Thank you and I appreciate all the information you give to us here.

  • Does symptoms ALWAYS correspond to lesions in the brain?

    I had a very prominent symptom (intense and weird sensation on the right side of my throat) that lasted around a year, that my neurologist discarded asa relapse as she said there was no lesion to correspond with it.

    Can you please give me your perspective?

    Thank you

    • MRI can only see lesions of a certain size , if the lesion is in a clinically important place you may notice it, many lesions are relatively unnoticed

  • There is something I like to see discussed, however, perhaps this blog is not the right platform? The subject is about ‘when MS care goes wrong’. Misdiagnosis, missed symptoms on examinations, procedures not followed correctly, etc..
    I do think it can be a important learning experience and framed right, it can be helpful to both staff and patients. I’m sure there are many with their own narratives about this.

    • Im not an MD edge member so cant see the post in the link. I prefer not to sign up to places to cut down the Junk email Was it about this paper

      Discontinuation of disease-modifying treatments for multiple sclerosis in patients aged over 50 with disease Inactivity.
      Kaminsky AL, Omorou AY, Soudant M, Pittion-Vouyovitch S, Michaud M, Anxionnat R, Guillemin F, Debouverie M, Mathey G.
      J Neurol. 2020 Jul 2. doi: 10.1007/s00415-020-10029-9

  • Have You met or heard about cases of allergy/intolerance (both food and airborne allergens) causing reactions with results (MRI) similar to Multiple Sclerosis? Or in other words – cases where allergic/intolerance reactions was causing MS relapse?

  • The Phase III clinical trial programme includes two identical Phase III trials in RMS (named FENhance 1 and FENhance 2) and one Phase III trial in PPMS (named FENtrepid). All three trials are targeting clinical disability progression and have a primary endpoint of 12-week composite confirmed disability progression (cCDP-12), with the addition of a co-primary endpoint of annualised relapse rate in the RMS trials. The PPMS study is the first study in this patient population to have an active comparator – OCREVUS – rather than placebo.

    Roche making a drug challenging their own other drug?! O_O
    I think this is the first case in MS…

  • Hi! With the approval of ofatumumab in the US, could you share any data and thoughts you have on vaccine readiness of ofatumumab vs. Ocrevus? I can’t find the raw data on how long it took in clinical trials for participants to repopulate their B-cells. I think I’ve read on this site that it’s 9 months – 3.5 years for Ocrevus, and the approval for ofatumumab says that “Data from RMS clinical studies indicate B-cell recoveries over the LLN in at least 50% of patients in 24 to 36 weeks post treatment discontinuation. Modeling and simulation for B-cell repletion corroborates these data, predicting median time to B-cell recovery of 40 weeks post treatment discontinuation.”

    My neuro is recommending a switch to ofatumumab because it would be easier to stop if/when a vaccine looks like it’s ready to launch, but it seems like it has a pretty long average repopulation timeline, and since it’s taken monthly, I’d almost always be closer to my last does of ofatumumab than I would be to my last dose of Ocrevus.

    • In the trials they dont repopulate their B cells because they get ofatumumab for every, but there is some data in the supplementary figure. However the median is 49 weeks this is in a paper by Bar-Or et al. on the MIRROR trial. The median for ocreliizumab is between 62-72 weeks the range was 27 weeks (7 months) to 175 weeks (about 3 years) and remember this is the CD19 population which is a mixed bag.

      The ofatumumab vaccinetion data will come from trial number NCT03650114 start date 2018. However it is bound to be the case that the vaccine responses are markedly inhibited just like ocrelizumab and rituximab. The data will probably first surface in the ofatumumab label in the USA (FDA). There is generatlly a section on vaccination with MS drugs it will be in there. This is not the case with the cancer application (AZERRA) where it was not reported but this treatment is a short course

  • YI01.05 – BTK signaling regulates real-time microglial dynamics and prevents demyelination in a novel in vivo model of antibody-mediated cortical demyelination

    According to multiplesclerosisnewstoday site it says that patients’ antibodies were given to mice and BTKi prevented/lessened damage. I see two things in this story: a good one and a bad one.
    The good one is that it confirms (even if in mice only) that damage is driven by antibodies so scrubbing the brain seems to be the right thing for the ultimate goal.
    The bad one is that BTKis that are capable of controlling both relapses and progression will be the pharma perfect drug: they will make patients depend on them for life controlling the disease but not curing it.

    Any thoughts from BartsMS team?

  • T time


    T cells take the lead in controlling SARS-CoV-2 and reducing COVID-19 disease severity

    with the bulk of the evidence pointing to a much bigger role for T cells than antibodies

    “Our observations could also explain why older COVID-19 patients are much more vulnerable to the disease,

    “With increasing age, the reservoir of T cells that can be activated against a specific virus declines and the body’s immune response becomes less coordinated, which looks to be one factor making older people drastically more susceptible to severe or fatal COVID-19.

    Old people dont have t time 🙂

    What we didn’t see was any evidence that T cells contribute to a cytokine storm, which is more likely mediated by the innate immune system.”

    Naïve T cells are inexperienced T cells that have not met their viral match yet and are waiting to be called up. As we age, the immune system’s supply of deployable naïve T cells dwindles and fewer cells are available to be activated to respond to a new virus. “This could either lead to a delayed adaptive immune response that is unable to control a virus until it is too late to limit disease severity or the magnitude of the response is insufficient,” says Moderbacher.

    If a vaccination is successful, vaccine-induced antibodies are ready to intercept the virus when it shows up at the doorstep. In contrast, in a normal infection the virus gets a head start because the immune system has never seen anything like it. By the time the adaptive immune system is ready to go during a primary infection, the virus has already replicated inside cells and antibodies can’t get to it.

    “Thus, these findings indicate it is plausible T cells are more important in natural SARS-CoV-2 infection, and antibodies more important in a COVID-19 vaccine,” says Crotty, “although it is also plausible that T cell responses against this virus are important in both cases.”

  • Metformin treatment linked to slowed cognitive decline

    A new research study, conducted over six years in the Sydney Memory and Ageing Study in 1037 Australians (aged 70 to 90 years old at baseline), has revealed an additional effect: individuals with type 2 diabetes who used metformin experienced slower cognitive decline with lower dementia rates than those who did not use the medication.


  • Ebv in the brain?

    The Epstein-Barr antibody paradox in
    Multiple Sclerosis

    Background and aims: Increased levels of serum and
    cerebrospinal fluid (CSF) antibodies against morbilli,
    varicella zoster and rubella, and increased serum antibodies
    against Epstein-Barr virus (EBV), are common features of
    MS. Paradoxically, several studies showed that the level of
    antibodies against the Epstein-Barr nuclear antigen 1
    (EBNA1) is low in the CSF, which may be due to immune
    evasive properties of EBNA1 or to low level of exposure of
    this antigen in the central nervous system. Our objective is
    to determine whether low CSF antibody levels against
    EBNA1 also apply to an immunodominant viral envelope
    EBV antigen, gp350.
    Methods: The level of anti-gp350 IgG was determined in
    serum and CSF in MS patients (n = 23) and healthy controls
    (n = 18) by an ELISA using a recombinant gp350 antigen
    The antibody index was calculated as adjusted QOD (QOD/
    (total IgG CSF/total IgG serum)).
    Results: The serum concentration of anti-gp350 IgG was
    higher in the MS patients. The CSF antibody index (adjusted
    QOD) for gp350 was significantly lower in the MS patients
    (0.070) than in the healthy controls (0.142, p<0.001). We
    obtained similar results if we included EBV seropositive
    controls only.
    Conclusion: Our finding of low CSF gp350 antibody index
    is consistent with other reports on the EBV antibody
    paradox in MS, arguing against antigenic exposure of this
    virus in the central nervous system. Interaction with EBV in
    MS pathogenesis might be confined to the peripheral
    immune system.
    Disclosure: Nothing to disclose

  • I have just been sent this very interesting article about Covid19 and the Bradykinin hypothesis, which sheds some light on why there are so many diverse reactions to the virus. Please could the Barts team read it and let me know your scientific opinion? I’m currently on Tysabri so the potential weakening of the blood / brain barrier is worrying…


  • I believe there was a course or series of events Nov 4 -6 . I was sadly not able to attend. Was /were event/s recorded ? Will it run again? I am interested in all of it but particularly the talk by Dr Ben Turner (?) on whether we are ready in UK to make HSCT first line of treatment. (Apologies: I am not 100% sure of title of presentation) .

  • I’ve been reading about the disease for a while and have been researching a number of treatments currently in development. I wanted to ask more about T-Cell vaccinations. I’ve been reading some literature and there seems to be a promising solution down that avenue but I found most of the research to be outdated (circa 2006 ish). While the studies have shown effectiveness, there hasn’t been a lot of traction for it, what’s your opinion on it and could we expect the research to come into fruition?

    • You research says it all…it faded away a decade ago, because the dreamers who could convince the academics that the approach was interesting and cherry picked their positive effects, could not convince pharma that this was offering anything useful. Importantly they went for the unmet clinical need and in doing so doomed their trials to failure. I must admit my attempts to repeat on Nature paper on vaccination didnt work, despite a number of attempts and visists to the authour’s labs. Some of the ideas were based on fantasy

  • I’ve been reading a bit about your attempts in figuring out the relationship between EBV and MS i.e. the INSPIRE trial or the possibility of using antiviral drugs for MS. It seems like a good lead but like you mentioned you’ve had problems getting traction. What if you analyze existing AIDS patients for EBV in order to try and streamline the drug selection process and hopefully get some data for INSPIRE 2?

    • There are very few HIV positive then MS positive people. Raltegrovir was not a good bet as it is a drug that stops integration but it was pharma funded. The haart therapy was the first choice

  • This is a general question to everyone who’d like to answer. In terms of ongoing MS research, what excites you the most?

  • Hi!
    I’m trying to find more info about Glossopharyngeal Neuralgia and MS, is there any info on one of your blogs about this subject?
    Hope to hear.

    • Maybe ProfG has mentioned there is a search function
      Glossopharyngeal neuralgia is a painful condition, affecting the ninth cranial nerve, rarely described in the course of multiple sclerosis.

      • Thnx for your reply Mousedoctor. I know it’s a painful condition, unfortunately…. It seems to be rare having MS indeed, that’s why I try to find more info about it. More info on what meds would help etc. Cannot seem to find it in your blog, sorry.

  • Brainstorming is always fun. MD previously mentioned that if the EBV vaccine works, it might not affect PwMS. While the real answer is we don’t know, what would the outcome of an EBV vaccine in conjunction with a dose of B-cell depletion therapy? Assuming B-cells are the main driver for demyelination, it could turn relapses to a thing of the past and focus on brain atrophy or uncover another agent so to speak.

  • I wonder if you can help explain this reaction to the AstraZeneca vaccine? My husband suffers from PPMS and had his first shot of the vaccine yesterday. Within 8-9 hours he lost complete use of his legs, much like happens when he has experienced flu or get overheated. Today he’s still bad, loss of feeling in hands and legs and generally feeling rotten.
    Is this related to a overreactive immune system due to MS? Or is there something else going on?
    Really interested to hear your views.

    • You have to understand that vaccines are equivalent to having a minor infection. I suspect this is what has happened he has developed a mild temperature and has developed conduction block that will improve over the next few days. Saying this it is important he does not have any other problems that have emerged.

      • Thank you for your answer!
        Would be good for people with MS to be made aware off by the healthcare professional administering the vaccine I think.

  • Here’s a question for the experts. If you had PPMS with evidence of new lesions in the brain in the last 12 months, would you opt for ocrelizumab or cladribine? Many variables I know in this kind of question, but on which of the two drugs would you chose to focus?

  • In the book ‘How the Immune System works’ by Lauren Sompayrac it says:” T cells isolated from MS patients can recognise a peptide derived from myelin basic protein as well as peptides derived from proteins encoded by both herpes simplex virus and the Epstein-Barr virus.” From Wikipedia: “Herpes cycles between periods of active disease followed by periods without symptoms.” and “Following active infection, herpes viruses establish a latent infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the nucleus of a nerve’s cell body.” So infection by the Herpes virus follows an episodic pattern, just like the common form of MS, and it resides in nerve cells. Has research been carried out to see if the presence of the Herpes in MS patients follows the same episodic pattern as MS? What I’m suggesting is that the episodic pattern of Herpes infection precedes and causes the episodic pattern of MS by the immune system producing T cells that can recognise peptides on the Herpes virus and on the myelin sheath. I’m aware that sadly there is no cure and no vaccine for Herpes infections. Is this an active area of research, or has it been discounted in the past?

  • Hi Team – I received the latest communication from Novartis on a DILI update for anyone on fingolimod. I would like to understand what your recommendation would be around this communication, meaning is there an age bracket that would be more susceptible to DILI, is there a study you could point me to in order to understand the implications. I am nearly 40, female, RR, and on fingolimod for around 5/6 years now. Thank you in advance, Kathrin

    • Once you have been on the drug more than 12 months this is unlikely to occur. The following is the EMA’s summary.

      • Cases of acute liver failure requiring liver transplant and clinically significant liver injury have been reported in patients treated with fingolimod.
      • The guidance for monitoring liver function and the criteria for discontinuation have been updated with additional details to minimise the risk of DILI:
      o Liver function tests including serum bilirubin should be performed before starting treatment and at months 1, 3, 6, 9 and 12 on therapy
      and periodically thereafter until 2 months after fingolimod discontinuation.
      o In the absence of clinical symptoms, if liver transaminases are:
       greater than 3 times the upper limit of normal (ULN) but less than
      5 times ULN without increase in serum bilirubin, more frequent
      monitoring including serum bilirubin and alkaline phosphatase
      (ALP) should be instituted.
       at least 5 times ULN or at least 3 times ULN associated with any
      increase in serum bilirubin, fingolimod should be discontinued. If
      serum levels return to normal, fingolimod may be restarted based
      on a careful benefit-risk assessment of the patient.
      o In the presence of clinical symptoms suggestive of hepatic dysfunction:
       Liver enzymes and bilirubin should be checked promptly and
      fingolimod should be discontinued if significant liver injury is

  • people with multiple sclerosis have already been vaccinated against covid. So far we have heard that vaccination is generally not a major problem for multiple sclerosis. is there any information as to whether the vaccination can permanently worsen the course of multiple sclerosis?

  • Phase 3b NOVA study.

    Hello, I notice that you have not commented on the results of the Nova study on the blog. It seemed like news to be given a lot of attention. Did I miss anything? Thanks for your comment.


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