Carpe diem

C

Barts-MS rose-tinted-odometer: ★★★★★

I love science; it is such a thrill. I think science historians will look back at 2020 and the impact COVID-19 has had on science and scientific publishing and will define a new scientific era as being AC19 (after COVID-19) and the other era as BC19 (before COVID-19). The reason why I say this is because some of the changes that COVID-19 has induced in the scientific process such as multi-stakeholder collaborations, data sharing, pre-publication, rapid repurposing and sharing of laboratories and technologies, sharing of hypotheses, thinking aloud, pooled funding, virtual meetings, distributed working, online consenting for trials, streamlining of the ethics and regulatory approvals processes for clinical trials, the reduction in red-tape associated with research, etc. is unlikely to go away. One could argue that all of these individual changes may be small, but add them together and the scientific process is going to be very different after COVID-19; in particular, it is going to be faster.

I sincerely hope the MS community taps into the success of the COVID-19 model of doing science. 

If I was in charge of MS Research, i.e. if I was the MS Research Tsar, I would have an open democratic competition to create a short-list of grand challenges in MS, i.e. hypotheses that need to be definitively tested at scale. I would then set-up an international steering committee of the deep thinkers in MS and make sure the MS politicians are excluded (those people of influence who often dominate these sorts of panels with their self-interests and blinkered and group thinking). These panels will have all their meeting in the open, i.e. lived streamed. The latter will make the scientific process transparent, which rarely happens and explains why so many MS researchers and research teams feel disenfranchised at present. 

This panel would then select principal investigators to run the research programmes to address the grand challenges. These PIs will need to buy into the grand challenge, i.e. have skin in the game, have a track record in project management and have the necessary peoples skills to get the project done. I would also make sure the projects are milestone driven to have some control over the trajectory and success of the projects. Projects will need to have predefined go-no-go milestones so as not to waste resources. 

I suspect one grand challenge will be vitamin D MS prevention studies. Although this is a daunting grand challenge it is essential that at some point the MS community takes up the challenge. The epidemiology and basic science around vD biology being in the MS causal pathway are so compelling how can we continue to ignore it?  

The following prepublication is very interesting. It shows, using a non-biased screening of compounds, that of  121 compounds identified with activity against SARS-CoV-2, the active form of vD, calcitriol, exhibits potent activity against SARS-CoV-2. In other words, active vD has antiviral effects. Could these antiviral effects have something to do with vD’s role in potentially preventing MS? Could these antiviral effects extend to EBV and infectious mononucleosis? What about vD and HERVs (human endogenous retroviruses)? 

I have so many questions and such limited time to answer them. My recent accident, and lucky escape, has made me realise how fragile life is; we all need to seize the day. Carpe diem!

Mok et al. Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis. bioRxiv doi: https://doi.org/10.1101/2020.06.21.162396

COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients. 

PS: Please support my new challenge: “Prof G’s crutches to 500 m Challenge“ we need to reach our target of £25,000 to support Dr Ruth Dobson and Dr Angray Kang’s COVID-19 MS Antibody Study. It is so important we get this study completed before COVID-19 becomes history. Please note that all of the money raised will go to Queen Mary University of London to support MS Research. Thank you.

CoI: multiple

Twitter: @gavinGiovannoni 

Medium: @gavin_24211

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

25 comments

  • This is an encouraging post Prof and I for one am glad that your time to reflect seems to be inspiring you to do push more limits of MS research as opposed to retiring to camps bay. Out of interest, is there an MS Tsar?

    • Re: “is there an MS Tsar?”

      No this is a hypothetical; nobody is going to create this position and in reality put in place a funding model as proposed. It is pie-in-the-sky thinking.

  • I agree; a most valid and brilliant idea.

    Here are others.

    Do Vit D levels have any relevance in persons of
    color in MS ? Blacks ? Probably not.

    How do we address sub-pial lesions on day 1 of
    the diagnosis?

    If we cannot treat optic neuritis how can we
    hope to treat a behemoth called the brain ?

    • Truly, there is no new thing under the sun. What has been will be again. ? vanity and vexation of spirit?

      The mouse doctor thinks that the great and the good thus rounded up would fight like cats.

      Report and recommendations National Advisory Commission On Multiple Sclerosis.
      US department of Health. Pub No NIH 74-534.
      Feb 11th 1974.
      (Fully funded……etc etc!).

  • Could 4000iu OD of vitamin D be the reason I completely escaped contracting covid from my husband recently, despite him coughing and sneezing ++ and no distancing in our house?

    An interesting hypothesis! Although I preferred imagining that I was magically immune in some way (despite my anti CD20)!

  • Prof G,

    Imagine you were stuck at EDSS 6.5 – your doctor tells you that you will gradually worsen over time. What would you want to achieve then? Stabilisation (no more worsening)? Some improvement (a couple of EDSS points)? These Grand Challenges are just pie in the sky – Vit D prevention study won’t happen, EBV vaccination study won’t happen. You have patients today who have had MS for 5, 10, 25 years – what’s on the horizon for them in the next 1-5 years? What are the Barts MS team hoping to achieve in the next 1-3 years ie to help patients today. As an MSer, I have little interest in the Grand Challenges that excite the minds of academics, I’m interested in having doctors who can properly address the disease I have and say “go away and enjoy the next 10-15 years” (as they did with my father and his kidney problems and my father in law with his heart problems). I look forward to the time when MS is a fully signed up medical disease ie the doctors can treat it effectively. At the moments it’s still a science disease – no one really knows what it is so the hypotheses and Grand Challenges can keep coming.

    • Sid, I think you wrong we will make the EBV vaccination MS trial happen. The vD trial is another story and needs a grand international coalition to get it done.

      • Looking forward to EBV vaccination MS trials! How does risk of long-term use of current anti-viral drugs compare to the risks of long-term use of anti-CD20 agents?

    • We are doing our bit for people with more advanced MS at the moment; i.e. ORATORIO-HAND, CHARIOT-MS, SIZOMUS, CLADRI-PLUS, CLAD-B and UNDER&OVER studies and have a few grants around more advanced MS to submit.

      • It occurs to me what SID wants is a cure, or certainty of the complete halt of progression, or real damage reverse therapies.

  • Vitamin D its a very hard subject to study

    You have efects all across a multitude of diseases from cancer to sleep disorders

    Have open 10 studies with very confounding results i would highlight 4 studies

    I suspect that in MSm vitamin D will not be a very good immune modulator, if it was great you would have all sorts of side effects….you don’t… so don’t expect the earth. Can it be of benefit, sure it can and you need to ensure good bone health.

    Mouse doc

    EBV and Vitamin D..reducing antibodies

    https://multiple-sclerosis-research.org/2017/07/ebv-and-vitamin-d-reducing-antibodies/

    High-dose vitamin D3 supplementation in multiple sclerosis is not associated with lower circulating neurofilament light chain levels

    https://www.professionalabstracts.com/ectrims2019/iplanner/#/presentation/1354

    Body mass index, but not vitamin D status, is associated with brain volume change in MS

    https://pubmed.ncbi.nlm.nih.gov/30429274/

    EPI005 – MULTIPLE SCLEROSIS AND VITAMIN D: CASE CONTROL STUDY MADE IN THE LATITUDE – 22

    Introduction: The peculiar geographical distribution of Multiple Sclerosis (MS) suggests the presence of an environmental factor in the genesis of this disease. It has been proposed for decades that vitamin D deficiency could be a possible explanation for the latitudinal gradient of MS
    Objectives: To evaluate vitamin D levels in patients with Multiple Sclerosis in the Fluminense Southern Region of Brazil
    Methodology: This is a cross-sectional case control study of a cohort in follow-up over the last 10 years
    Results and Conclusions: Results:Data from 50 patients and 50 controls were obtained. The female sex was more frequent. The mean age of the two groups is found in the 5th decade of life. In the group of patients the median EDSS was 2, ranging from 0 to 8.5 and the average disease time was 8.7 years (± 7.5 years). There was no significant difference between the mean serum levels of vitamin D between the groups studied. However, the majority of participants in both groups had serum levels of vitamin D below normality. There was also no difference between these two groups when assessing the time of daily exposure to sun, season of birth and vitamin D status. Conclusion: In Brazil there is great availability of solar radiation. Despite this, the majority of study participants had serum levels of vitamin D below those considered normal. Further studies are needed in different populations for greater conclusions.

    • Luis, you are confusing vD MS disease-modification with vD MS prevention studies. These are very different hypotheses and I would be surprised if disease-modification would get democratic support to be a grand-challenge, whereas MS prevention has already achieved that status, but has never been taken forward.

  • We are here but for a mere blink of the eye, and all we do is largely fumbling and thrashing around. In MS research, we can’t seem to agree on the goal, nor on the method to get there. Kind of like life itself.

    • So very true.

      Have (s) vs have not (s).
      Kind of.

      Those with 7T MRIs publishing by the minute, and grabbing grants by the second. As it were.

      And then there is the old boys’ network.

      Data…. not a single drug company shares it’s post marketing data.

      More importantly they are the very folks who sponsor a pivotal study, for example, analyze and publish the data via some ‘famous names’ in top notch journals. How does anyone beat that?

      Professor G’s hopes and aspirations not withstanding, I don’t believe anything will change once the pandemic dies down with vaccinations or whatever.

  • Nothing like becoming The Patient to put the Whole Picture Together.
    Inspiring ✍🏼
    Make sure you get a Lot of Voices from Patients.
    Please check out Apollo Neuroscience device and the Oura ring.
    I’m finding ever so minute changes for the positive.
    Monitoring my Heart Rate Variability… if nothing else, it amuses me to think words I write Are potentially helpful to another hurting person like myself. Nothing like a Disability to Force You to ReChannel your Energy.
    😎

  • The progressive alliance arose in part from the Meet The Scientist initiative we set up many moons ago. It was at these meeting we collected the MS community’s views on what was lacking in MS research. We sent these to the UK MS society and the idea was born. I could be wrong and happy to be corrected but MD and MD2 and GG were there at it’s inception.

    • That is just the beginning in my view and it is a great thing the alliance is in place. To do what ProfG says in its post we should work as a community. Starting from the alliance we could build a global network that can join funds, forces and know how to advance together towards a cure. The fact that we are starting to say that MS is progressive from the beginning can turn the alliance for progressive MS to the alliance for the MS (as one disease). As a first step we should remove the classification and at that point a network is already set. Running a trial across different countries means sharing the workload, the costs, the risks and the benefits at the price of a larger organizational effort to frontload. If the foundations to ease this process are already set then much more studies will become possible in a shorter time leading sooner to improvement in few years.

  • Dear professor,

    Could you make a study for ms in which an EBV vaccine is used to see if it can cure ms using potentially the moderna vaccine for EBV ?

      • Yes it should. Antiviral medications work when EBV is replicating ( lytic phase ), a vaccine would teach your body to do the same job ( antibodies ) that inhibit the viral entry into cells.

        Likely scenario once a potent vaccine for EBV arrives :

        The only question is would a vaccine work for the remaining EBV infected cells ( B cells infected with EBV ) within the central nervous system but a vaccine at the very least should be effective at completely stopping relapses as the viral load decreases over time within the blood stream.

        Even if a vaccine is not completely effective, an antiviral medication ( that works for EBV ) capable of reaching the central nervous system will eliminate the EBV in the central nervous system and blood stream and stop ms in its tracks. Once enough of the virus has been cleared within the central nervous system a vaccine might be enough to teach your body to eliminate it and the need for an antiviral medication might no longer be needed.

  • Its worth noting that the experiments were done with cell lines (a highly artificial environment) and concentrations of calcitriol of 10uM – that is a pharmacological rather than a physiological dose – around 1 million times higher concentration than the picomolar doses that occur in human serum, and likely to be toxic to humans.

  • ..or they may feel disenfranchised because the Kung Foo flu has shown how it is greed and pure greed that hinders the search for a cure; not just for MS but for so many afflictions
    Research for actual cures and vaccines can be done quickly if the will is there, so maybe that’s why it is disconcerting for them..

    Your plan is a grand one – good on you for getting back on the horse; but a definitive cure by way of vaccine perhaps would be much more welcome
    I’ve been chomping Vitamin d for years And it hasn’t made a blind bit of difference, (may be it would have done if my mother had been given supplements when she was pregnant with me- prevention is way better than treating right) and I am now fcuked regardless with no hope of recovery…

    But i hope yours is speedy u legend – so still made a donation to you Don G

    Who needs to be labelled a Tsar when you actually are the Don

    Just sayin

By Prof G

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