The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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Recent conference in Stockholm. Dr Bansal's talk, youtube Nov 19.

Discussion in 'General ME/CFS News' started by aimossy, Nov 23, 2014.

  1. aimossy

    aimossy Senior Member

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  2. Snow Leopard

    Snow Leopard Hibernating

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    Thanks. Disappointed that the Youtube image shows the 'persistent stress' slide though.
     
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  3. aimossy

    aimossy Senior Member

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    Not my doing I can promise you :) I just came across all these.
     
  4. alex3619

    alex3619 Senior Member

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    Super summary:

    Higher levels of "latent" viruses.

    Decreased NK function.

    Increased beta adrenaline receptor function.

    Glucocorticoid resistance due to a bad (low) glucocorticoid receptor alpha to beta ratio. This might translate to a functional Addisons disease. Glucocorticoids don't work properly.

    Low specificity antibodies? Preliminary evidence of brain and mitochondrial autoantibodies.

    The beta adrenaline response and the glucocorticoid resistance might in combination lead to a biomarker. They may also be targets for treatment.
     
  5. alex3619

    alex3619 Senior Member

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    Let me add that we already know that genetic defects in cortisol binding globulin induce a CFS-like syndrome. I was in one of those studies but did not have one of the suspect snps.

    Thinking about this model it touches upon many of the issues that I think a model of ME requires. Very very interesting.

    Bansal also thinks that a complete therapy might require antivirals.
     
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  6. aimossy

    aimossy Senior Member

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    I liked that he was clear about contradictory results. I was interested in a fair amount of the talk. Also about the fact that they have been looking at some autoantibodies I think regarding the hypothalamus? I cant remember now if I am using the correct word. I thought this was at proposal stage still based on something I read in a not long past. It looks like they have been doing some investigation.

    @Jonathan Edwards he talks about the B cell work at UCL although I don't think he says too much about it considering its being worked on. I have just tagged you to let you know this was here if you were interested about this talk happening. I still cant figure out where this conference came from except that it was in Stockholm by the looks of it. There are some other youtube videos from this conference.
     
    Last edited: Nov 24, 2014
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  7. Forbin

    Forbin Senior Member

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    I thought it was interesting that he linked the onset of the immune dysfunction to getting an infection during a period of high physical and/or mental stress. This seems consistent with my case. I was had been working 16 hour days for 4 months when I came down with the flu, and I probably returned to work too quickly. Oddly, ME kicked in a few weeks later while I was vacationing (which has always suggested to me that the onset could be a "slow burn").

    Some of the locations of the outbreaks - hospitals, military bases, etc. - suggest the possibility of physical/mental stress being present, but why would so many people in Lake Tahoe be under such stress? Why would the kids in Lyndonville? Some not insignificant portion of people in any flu outbreak are going to be under physical/mental stress, so the question might just as likely be why do so few people get ME/cfs?

    Genetics perhaps... perhaps some people have a previous infection that the immune dysfunction no longer properly controls (the EBV connection?)... perhaps something in the nature of the infection itself - maybe if a stressed out body mishandles the initial infection things start to go wrong. I'll have to re-watch the video. There was a lot of interesting information in there.

    [The over-response to adrenalin also rings a bell, although I always imagined it was an over-production of adrenalin rather than an over-response.]
     
    Last edited: Nov 24, 2014
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  8. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Yes, I looked at this over the weekend, after IiME had flagged it up for me. I think it was a European ME meeting in Stockholm, just recently. I had also talked with Amolak about some of these things on Friday.

    I thought this was a very impressive and balanced overview. I agree that the emphasis on the need for repeatable results was good. He is talking about autoantibodies to brain stem/hypothalamic structures. I don't think he would want people to read too much into that yet but it sounds very interesting - and clearly they have started work. The collaborative B cell work is still blinded so there is nothing that can actually be reported yet.

    I think the cortisol resistance idea is fascinating and well worth further exploration - I very much agree with Alex here. And Alex's mention of a genetic resistance giving a CFS-like syndrome is also very interesting. My devil's advocate self says 'But how could this explain poor Justy's experience at St Pancras (so sorry to hear about that). Just having cortisol resistance shouldn't make sensory stimuli intolerable should it?' But maybe it can. Maybe if one part of the brain thinks there is enough cortisol and another part is getting messages saying there is none it flags up some sort of automatic danger message. An autoantibody to some link in the HPA axis would be such a simple explanation.

    There is also this hint that low affinity/specificity antibodies and maybe IgM persisting might be involved - which might explain the paradoxical results with EBV responses Dr Scheibenbogen finds.

    And @wdb and @Bob, I finally figured out what I was doing wrong on the tagging - thanks.

    For me the really positive thing about this presentation is that I think it is a manifestation of a growing European collaborative effort to get everyone on the same page and interacting. And this sort of broad balanced view is exactly what is needed.
     
  9. Helen

    Helen Senior Member

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    Seminar program:
    http://www.meassociation.org.uk/2014/08/invitation-to-stockholm-seminar-on-paediatric-mecfs-12-november-2014/

    Talks presented in English are posted in this thread:
    http://forums.phoenixrising.me/index.php?threads/invitation-to-stockholm-sweden-seminar-on-paediatric-me-cfs-12-nov-2014.32335/
     
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  10. Gijs

    Gijs Senior Member

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    Professor Edwards: ''think the cortisol resistance idea is fascinating and well worth further exploration - I very much agree with Alex here. And Alex's mention of a genetic resistance giving a CFS-like syndrome is also very interesting. My devil's advocate self says 'But how could this explain poor Justy's experience at St Pancras (so sorry to hear about that). Just having cortisol resistance shouldn't make sensory stimuli intolerable should it?' But maybe it can. Maybe if one part of the brain thinks there is enough cortisol and another part is getting messages saying there is none it flags up some sort of automatic danger message. An autoantibody to some link in the HPA axis would be such a simple explanation.''

    I like simple ideas. As you describe. It does seem as if an alarm is sounding constantly in ME / CFS. The body therefore can not relax. Like relaxing is dangerous. So it feels.
     
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  11. Bob

    Bob

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    This is a very interesting video. Don't be put off by the first two minutes, which gives a very brief but rather unhelpful (in my opinion) discussion of precipitating factors. After that, he quickly and firmly dismisses the idea of CFS/ME being a psychosomatic illness, or a fear of activity, and then he moves onto some really interesting and meaty immunological discussions, research and theories. Discussions include: the nature of the illness that he sees in his clinical practice; his department's research program; his opinions about the nature of the illness; and his opinions about how it may be treated in the future. He's looking at: antivirals; EBV viral particles; NK cell dysfunction; B cell abnormalities; auto-immunity to cell nuclei in the hypothalamus; autoimmunity to mitochondria; and much more. His research program includes: a leaky gut study; the mechanisms of post-exertional malaise after both physical and cognitive exertion; and more. This is a serious man with a serious program. I'm impressed.
     
    Last edited: Nov 25, 2014
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  12. aimossy

    aimossy Senior Member

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    Thanks @Jonathan Edwards I had hoped you would have some commentary/thoughts on it.

    I was wondering could this be it! Regarding autoantibody and HPA axis you mention - somehow connecting to the cortisol resistance. I thought no way that's too black and white this is way more complicated. I'm really interested to see what comes from the work into the autoantibodies to those parts of the brain and think that was why I was excited to come across this talk.

    The cortisol resistance, it's hard to grasp with a funky brain. I would have to watch that talk twice to get it in my head properly or see the research all in written form.
    Is that saying in a basic way that you wouldn't be utilising cortisol in the body adequately? That's what I took it to mean.
    My thoughts when listening were 'could that be a reason for not tolerating a lot of things including stimuli, pressure, stress and exercise' because I thought it could cause that but again probably too simple in thinking. Anyway, thanks for the comments.
     
    Last edited: Nov 24, 2014
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  13. Bob

    Bob

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  14. Bob

    Bob

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    Thanks aimossy. I only know the details presented in the slide. The slide is right at the end of the presentation if that's any help for you. Like you, I've got to re-watch the video to try to absorb some of the info. I might make some notes and post them here later.
     
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  15. aimossy

    aimossy Senior Member

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    Thanks @Bob I think the leaky gut one is the IiME one I could be wrong. I am wondering if it actually less of a focussed programme but more of bits of collaboration with different charities and researchers if you see what I mean!
     
    Last edited: Nov 24, 2014
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  16. Simon

    Simon

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    Delighted to hear that a lab (rather than clinical trial) is blinded. I got the impression blinding wasn't that common, certainly it doesn't usually get mentioned in papers - but is this sort of thing now standard practice?

    Very interesting, do you have a link to this work?
     
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  17. A.B.

    A.B. Senior Member

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    The idea that CFS is a form of Addison's disease isn't new:
    Chronic fatigue syndrome: a form of Addison's disease

    I don't think the author is right on all points but the similarity is indeed striking.

    A problem in utilizing glucocorticoids rather than producing them would also explain why giving cortisol to CFS patients, while helpful, isn't all that effective in the end.
     
    Last edited: Nov 24, 2014
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  18. Bob

    Bob

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    He only mentioned it briefly, but he mentioned that he is seeing a high rate of joint hyper-mobility (flexible joints) in his clinic. (I have slightly flexible joints - it's a genetic condition common in my family - so it interests me.) Joint flexibility is related to Ehlers–Danlos syndrome (EDS) which is caused by a defect in connective tissue (e.g. tendons) which makes the tissue soft and flexible. EDS patients have increased rates of degenerative conditions and auto-immune conditions. Looking at the symptoms of EDS, my guess is that epithelium tissue is also affected.

    I have a theory about this in relation to ME/CFS. Perhaps this soft tissue gives rise to easily damaged epithelium and membranes etc. (e.g. brain-blood barrier, gut lining, nasal/sinus membranes, veins/arteries etc etc etc.) Perhaps when we have stress-insults or infections, these membranes or epithelium tissues become excessively porous and fail to give the expected protection from infections or pollutants, which leads to an excessive immune insult and subsequent immune dysregulation.

    It's just an idea. Not everyone with ME/CFS has flexible joints so it's not the answer, but it might give some clues about the origins of the immune dysregulation in ME/CFS.
     
    Last edited: Nov 24, 2014
  19. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    interesting.

    Good to see he mentions the role of viral infections as well as the T cell abnormalities found in cfs/me and the decreased nk function which can play a role in allowing viral infections to continue causing symptoms, this seems to be controversial of late.

    The TH1/TH2 theory has copped abit of flack lately but i see it was used in this summary and explained that it isnt 100% accurate, but a guide.
    .
    B cell dysfunction was also mentioned and possibly playing a role.

    Many of us have known for awhile about adrenal dysfunction which probably leads to the autonomic dysfunction with pots/oi symptoms.

    Its a good all round laterally thought summary, that i think many of us have gathered from all the research the patient group here have gathered and posted somewhere on this forum. Hopefully this helps to educate many doctors out there to help find treatments and stimulate further research for our cause.

    Also glad he mentioned that it wont be just a silver bullet treatment but probably many of the abnormalities discussed would play a role in treating cfs/me

    I cant quite recall if it was Sweden or not but Dr Peterson did a similar talk at the start of the year. Thats promising to see the Scandinavian countries taking further interest in cfs/me and also looking outside their own research to further help find answers.
     
  20. Snow Leopard

    Snow Leopard Hibernating

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    I personally think most of these HPA axis findings are superficial and haven't been properly in the depth required to lead to any sort of conclusions.

    The low levels of cortisol, has long been speculated to co-exist with increased GC Receptor expression or activity (which would allow overall homeostasis to be maintained). Which is of course the opposite of GC resistance.


    What do we actually know? Well studies of GC receptor expression activity, affinity etc have led to contradictory results. We should also consider the role of (low) vasopressin which has also been implicated in some of these HPA axis studies. We also know in general that there are interactions between vasopressin receptors and beta adrenal receptors. Specifically, if you had low vasopressin, then you'd expect higher vasopressin receptor expression to compensate, that would in turn inhibit beta adrenal receptor activity. There seems to be no discussion of this in the CFS literature. Interestingly, β-2 adrenergic receptor gene expression has been found to be low in several studies, but has a greater than increase in expression post-exercise, compared to sedentary controls.

    The cytokine studies do tend to show a trend overall - towards an anti-inflammatory profile, with IL-10 in particular.

    There is evidence for downregulated cellular stress responses/signalling cascades, despite evidence of increased oxidative stress. Expression of some of these kinase pathways directly affects the expression of genes that play a role in NK cell lytic activity.

    Conclusion - there are lots of possiblities out there, some in-depth work needs to be done to uncover the overall picture.
     
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