Wednesday, 11 November 2015

ResearchSpeak: preventing MS

Shame on us; why haven't we started any MS prevention trials? #ResearchSpeak #MSBlog #MSResearch

"One the research themes to come out of the MS Society's James Lind Alliance scoping exercise was 'MS prevention'. Can we prevent MS? The UK MS Society is hosting a MS Prevention meeting tomorrow at Heathrow (see programme below).  We know an increasing amount about the causal pathways in MS and other autoimmune diseases and it is becoming increasingly clear that targeting the known environmental factors in MS is the obvious way to go. 

The big questions are:

  1. How do we stop the population smoking, or at least people who are at high-risk of getting MS from smoking?
  2. Is it vitamin D deficiency, or lack of sunlight exposure, the risk factor for developing MS and other autoimmune diseases? Is low vD levels simply a surrogate of low sunlight exposure and it is the latter that is the risk factor?
  3. How do we design a vitamin D prevention trial? Should we focus on the general population or high-risk groups (1st and 2nd generation family members of MSers)? What dose of vD should we use or do we need to supplement to a target (e.g. >100nmol/L)? Is it ethical to do a placebo controlled trial? Could we use 400IU of vD (the current RDA) as the comparator? What about the timing of vD supplementation; should it be started in utero, childhood, adolescence or early adulthood? Can we simply supplement the population and look at disease trends?
  4. Should we be partnering with other disease groups; for example the type 1 diabetes community? If we use type 1 diabetes as a surrogate prevention  trials will report out decades earlier than with MS.
  5. EBV; how good are the current EBV vaccines? Do we need new vaccines? Is it safe to prevent the population from acquiring EBV? EBV is one of our most co-evolved viruses, it is part of our metagenome. Preventing people getting EBV may have consequences. What role does EBV play at the population level? I suspect it may play a role in immunological memory and that stopping the general population from being infected with the virus will have consequences.
  6. Would simply preventing people getting infectious mononucleosis (IM) be sufficient to lower the risk of developing MS? Is the EBV-IM MS link simply an association and not causal? In other words the observation that people who develop IM are at increased risk of MS may simply indicate that these people have something wrong with their immune systems that also happens to predispose them to getting MS. I don't buy into this latter argument, but it is out there, nevertheless.
  7. Should we developing a treatment for IM? Will treating IM successfully lower their risk of someone getting MS? What happens to the immune system post-IM that predisposed people to getting MS?
  8. What about EBV itself? Is there a mutant EBV variant that causes MS and/or other autoimmune diseases? 

As you can see there are more questions than answers. What I do know is that if we don't act now  the next generation of MSers will look back at us and say 'why didn't you do something about it, if had done I may not have MS today'. In 2015 we know enough about MS and its risk factors to be starting prevention trials. Doing nothing is simply not acceptable."

"It is a great pity George Ebers is not attending this meeting. George and I have had many a long conversation about MS prevention. George is a deep thinker and has some brilliant ideas about how to do vD MS prevention trials at a population level." 

23 comments:

  1. I'm sorry to hear about George's passing

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    1. He's not Dead, He is retired and Living in the Middle of Nowhere in Canada

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    2. Maybe he wanted to live in the country with the highest prevalence of MS or he has a love of hockey.

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    3. is alastair compston dead? i heard he has taken a turn for the worse.

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    4. I hope not, I have heard that prof compston has a battle with health issues and we hope he beats them

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  2. No talks from Team g? Where is prof gold?

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    1. was he invited? he knows more about viruses than any of these guys

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  3. Should researchers be looking at other causes of glandular fever? Is the following correct?

    Glandular fever may also be caused by Cytomegalovirus and Rubella (German measles). Glandular fever-like symptoms may also appear in cases of toxoplasmosis, a parasitic infection.

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    1. I believe that 'glandular fever' here is being used as a description of symptoms rather than a disease. It is the Epstein Barr virus that infects most people and it is infection with this virus that appears to be requirement for the later development of MS. There is more than one variant of the virus, so it may be one particular variant that causes MS.

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    2. Why would you use 400IU a day of vitamin d for anyone, you will do harm for no good reason. The Royal College of Paediatrics and Child Health recommends 400 to 1000IU a day for babies (1 month to 18 years), with no known deficiency. They go up to 10,000IU a day for those with known deficiency.

      The RDA in the USA of 600IU a day has been shown to be wrong due to an error in calculating it. The error was to consider the distribution of the average 25(OH)D levels from many studies rather than the actual individual distributions. It appears to be out by a factor of 10.

      I believe that the MS occurrence rate in this country has been stable for a long time so why would you need a control.

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    3. The papers were saying glandular fever is mostly caused by EBV but may also be caused by Cytomegalovirus and Rubella.

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  4. I think the risk factors you list: smoking, EBV, low vit D, should be studied studied in the context of their effects on the blood brain barrier. The mabs target lymphocytes thereby preventing egress into the CNS. Certain gut microbiota have been studied for their effects on the BBB. Restore the integrity of the BBB and find the source of its compromise in MS. I realize.....easier said than done.

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    1. As EBV infects B cells and vitamin d is important in controlling infections, the effect is likely to be in the immune system. EBV infected B cells can disrupt the immune system. With EBV induced lymphomas you see disruption of the immune system including severe itching in parts of the body a long way from the lymphoma and also effects like fatigue/brain fog long before the lymphoma is big enough to be detected. So the starting point of the cascade that leads to MS may not even be in the brain or spine, but in a lymph node somewhere. There may also be very few damaged B cells starting the process.

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  5. Just some published data from the MS Trust:

    "The report highlights the critical challenges facing MS care. The data reveals that more and more of MS specialist nurses’ time is required to support people taking disease modifying drugs – and the MS Trust is aware of growing pressure to increase the UK’s comparatively low treatment rates. However, half of the people living with MS in the UK have progressive forms of the disease and are not eligible for these treatments."

    Prof G can hark on about progression rates improving, but there it is: 50% of MSers have become progressive in Britain and adult social care and access to treatments are being eroded. Things are getting much worse, not better.

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  6. Dear Prof G, Has anyone looked at MS data from the Republic of Ireland to see if there is any impact yet from the smoking ban? The smoking ban went into effect there in March 2004. Has this had any impact on the number of folks diagnosed in, for example, Donegal yet?

    What are the current tests run on children at 6,12, 18 month etc; is a vit D level part of that check? Just adding a vit D check would increase vit D intake.

    What part of the physical exam we make a self test? Can you stand on 1 foot for 30 seconds? If no see the doctor. Am trying to think of a way to implement the VEP test on a smart device.

    To significantly reduce the number of folks being diagnosed in the future, we could assume that targeting only 2 of the above would be sufficient. Society is targeting smoking, what could we do to increase vit D?

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  7. When it comes to the subject of the tests for vitamin D check it is alleged that it is complicated because it is expensive to perform. I think maybe try to find a way to cheapen the tests to check vitamin D levels in the general population, because with respect to genetic factors that confer susceptibility to MS are more difficult to be measured because they are not 100% determinants (as far as I know) and are extremely expensive tests ... it is for those who have symptoms similar to infectious mononucleosis that are also made diagnosis need it, as well as tests for anti-EBV antibodies ...

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  8. I posted earlier but must have included too much details and broke the rules - there are new techologies emerging in the blood testing space that will reduce the cost of testing.

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  9. Sorry MD,

    Am very excited about the changes coming in health care. To think that soon we will have access to more data about our bodies is really exciting. In my question above I would like to see what impact the smoking ban has had in Ireland since that was the first country and will be indicative of other countries. We could compare Derry and Donegal since both counties are on different sides of the border and therefore implemented the no smoking law years apart. But have the same Vit D exposure.

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  10. Are the presentaties of this MS prevention meeting going to be published?

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