Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
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A New Decade of ME Research: The 11th Invest in ME International ME Conference 2016

Discussion in 'Phoenix Rising Articles' started by Mark, Jun 14, 2016.

  1. Mark

    Mark Former CEO

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    I think it's quite fair of you to point out that Hanson's study with the LPS findings had basically the same number of patients and controls as KDM's. When you halve that group, though, and compare Belgian and Norwegian groups and note the differences, I think it's getting way too small to conclude anything from that comparison, especially because it may just reflect different dietary factors. I think with all these things it depends on the detail of the findings as to how the sample size affects the results. If you have a clear and stated prior hypothesis about factor X and study 40/40 and find all the patients have X and none of the controls do, then that obviously means a lot more than a study trawling loads of different data points on 40/40 and simply reporting the results. In the small study that Hanson reported, there were several data points that fitted together to give stronger confirmation of the LPS findings, and they were looking at far fewer variables I think. So I think it's a bit stronger for that reason, but still very preliminary really.

    I do think Simon's right to urge caution in interpreting the results of small studies. Yes, an awful lot of ME/CFS research has been on small sample sizes, and that's a big part of the problem. Non-scientists interpreting results are liable to give them much more weight and read more into them than a scientist should. Small studies by one group suggest potentially interesting lines of inquiry, I would say, and not much more than that. Lots of small studies might add up to something, but even there, one would have to know about all the other small studies with null findings that were never reported in order to make an informed judgment overall. Because we don't have mandatory registration of trials before they begin, and mandatory publication of results, the whole situation regarding the quality and reliability of published science is highly unsatisfactory to say the least. The best one can really say about these small studies is that they are 'interesting' - and many things are 'interesting'...
     
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  2. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Chinese whispers I fear.

    A presentation at the pre conference colloquium indicated that a large ME/CFS cohort had been compared to controls in terms of serological evidence of such infections and no differences were found. The data are several years old I think and were not published simply because it is frustrating trying to publish negative findings. This I think is a huge problem for ME research because there are lots of negative data lying around unpublished for this reason. And negative data are often the most powerful.
     
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  3. msf

    msf Senior Member

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    Well, I´m not a statistician, but I will wait until the Hanson study is published before I compare it with the KDM study.
     
  4. lansbergen

    lansbergen Senior Member

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    There should be a place where these data could be published.
     
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  5. duncan

    duncan Senior Member

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    Agreed.

    Negative studies can be essential. They can prove a connection. They can disprove it. Both of these effects can - once in a while - be evidenced inadvertently, in counterpoint to the conclusions reached or stated by the authors. Negative studies can sometimes reveal more about bias or intent, too. Just look at the notorious three RCTs for extended abx for Lyme as an example.

    I'm not saying that would have been the case here. Just bemoaning what I know is obvious to many.
     
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  6. Simon

    Simon

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    Shorter version of @Mark's excellent piece - with links direct to each speaker's section

    I've written this for #MEAction but it might be a while before it's posted, so thought I'd put here too. Nb click on the title links to go direct to the relevant section of Mark's talk:

    The 2016 Invest in ME Conference – great write up on Phoenix Rising

    Phoenix Rising’s Mark Berry was at the recent Invest in ME conference and has written an excellent report: A New Decade of ME Research: The 11th Invest in ME International ME Conference 2016

    As the article is quite long, here are some tasters (my summaries, with quotes from Mark’s article) to whet your appetite for the feast, which concludes with Professor Ron Davis’s talk.You can click on the titles to go direct to the relevant section in Mark’s report.

    Dr Vicky Whittemore hails ‘new dawn’ at the NIH for ME/CFS

    Whittemore acknowledged historical problems at the NIH, such as the “shocking and disappointing” funding levels and outlined the NIH’s emerging agenda for the illness including the ‘deep dive’ intramural study.

    ‘She said that her “hope and vision” was to return to IiME in the next two years and present a graph showing levels of government funding for ME/CFS research “off the charts.”’


    Clinical Diagnosis of Myalgic Encephalomyelitis

    Professor Olli Polo talked about how he diagnoses ME/CFS, and said that symptoms affect the whole of the sympathetic trunk, making ME/CFS a whole-body condition that doesn’t fit well with the prevailing model of medicine. He also said that many of his patients had signs of connective tissue disorders.


    Autoantibodies to neurotramsimtter receptors in CFS/ME - Professor Carmen Scheibenbogen

    Scheibenbogen reviewed the evidence for autoantibodies playing a role in ME/CFS, and discussed her recent finding that patients had more autoantibodies than controls against two types of neurotransmitter receptors: beta-adrenergic and muscarinic acetylcholine receptors. She noted that stimulation of these receptors could cause familiar ME/CFS symptoms.

    Her research also found that responders to rituximab in the Fluge and Mella trials had reduced levels of these antibodies after treatment, while this wasn’t seen in non-responders.


    Immune regulation in patients with ME - Dr Jo Cambridge

    Cambridge worked with Professor Jonathan Edwards to develop rituximab as a treatment for rheumatoid arthritis, and got involved in ME/CFS research following those promising rituximab pilot studies in Norway.

    She discussed how rituximab works in various autoimmune diseases. It kills most B cells and may work in ME/CFS either because it stops B cells turning into the antibody-producing factories called plasma cells (cutting off supplies of autoantibodies), or through stopping the interaction between B cells and T cells, which are another key type of immune cell.

    PhD student Fane Manseh, who works with Cambridge, presented his work studying ME/CFS patient B cells in the lab, looking at what controls their development and antibody production, and how they interact with T cells.


    Gut Virome in ME - Professor Tom Wileman

    You’ve heard of the gut microbiome, and the gut virome is part of this: it’s all the viruses that infect the bacteria in the gut (“Every flea has a flea that lives on a flea”). Interactions between the gut microbiome and the body can affect inflammation, and the ‘Virome hypothesis’ says that the gut virome can play an important part in triggering this inflammation leading to disease.

    Wileman has studies the virome in IBS, and found that reduced diversity in the virome (fewer different types of virus than normal) is linked to IBS. The virome may provide a biomarker in diseases, including ME/CFS.

    Invest in ME-sponsored PhD student Daniel Vipond is currently exploring the gut virome in ME/CFS patients.


    Receptors and intracellular signalling - Professor Don Staines

    Staines, of Griffith University, discussed the team’s recent work on receptors that play an important role in cell signalling. Their previous research had identified an association between a genetic variant of the ion channel receptor, TRPM3, and ME/CFS. When the TRPM 3 receptor is activated, it briefly lets calcium into the cell, which is a common way the body uses to send a signal.

    Recently work from the group showed patients had reduced levels of the TRPM3 receptor in B cells and natural killer cells, which together with the genetic variant may affect cell functioning: they found reduction in calcium levels within cells. Staines said his group believe that ion channel receptor function, and calcium signalling problems, could be causing ME/CFS.

    Staines said they have many more papers on this subject to follow.


    New European research networks launched

    Professor Simon Carding introduced EMERG, the European ME Research Group that was launched last autumn. It’s a network of research groups which aims to jointly define a co-ordinated research strategy. EMERG is already working to improve research with expert groups looking at clinical diagnosis and stratification, biomarkers and standardising how different research groups prepare samples.

    A separate network, EUROMENE – for individual researchers rather than research groups – was launched in Easter this year and has secured 6 million Euros in funding. EMERG and EUROMENE have already met up and will work in complementary ways.

    Early feasibility projects are looking at infectious origins (environmental and microbiome alterations), and clinical trials and supporting research (e.g.,rituximab).


    Pathogen Discovery in ME – Dr Mady Hornig

    Hornig explained how the group at Columbia University are working to identify pathogens and triggers for ME/CFS.

    “Much of her wide-ranging and complex presentation aimed to explain why her group’s model of ME is an immune-mediated brain disorder, with a significant connection to the gut. When the microbiota (gut microbes) are disordered, disorders of brain function are among the many consequences.”

    Changes in the gut microbiota could trigger autoimmunity, she said, and also have an effect on the brain, for example by affecting the levels of tryptophan, a molecule that’s needed to make some neurotransmitters (infections can affect tryptophan levels too). In short: it’s complicated.


    The Search for Biomarkers for Myalgic Encephalomyelitis - Professor Maureen Hanson

    Hanson talked about her study with Susan Levine using 49 ME/CFS patients to search for biomarkers in the gut microbiome. They’ve made two interesting findings. The first is a big increase in blood lipopolysaccharide, LPS, which could be due to bacteria or bacterial breakdown products from the gut crossing into the blood. The second finding is a shift in microbiome profile, with more bacterial species reported to be pro-inflammatory, and fewer bacteria reported to be anti-inflammatory. There was also a “loss of species richness” i.e. fewer different types of bacteria in patients. The microbiome profile has potential as a biomarker, she said, and her group will do more work to develop its potential.

    Hanson commented it was hard to square these findings with a psychosocial model of ME/CFS.


    Molecular Biomarkers of Myalgic Encephalomyelitis

    Professor Elisa Oltra is looking for biomarkers among microRNAs, small RNA molecules that play a key role in regulating gene expression that have been established as proven biomarkers of other diseases, she said. Her group have already found microRNAs with biomarker potential in a small study of Fibromyalgia patients who also had ME/CFS, and they are working on a replication in a larger sample of patients.


    Exercise Testing and Orthostatic Tachycardia - Professor James Baraniuk

    Baraniuk reviewed the changes in diagnostic criteria for ME/CFS, fibromyalgia and Gulf War Illness. He noted that fibromyalgia criteria had ‘drifted’ from the original versions, as had ME/CFS, but he praised Carruther’s focus on the key ME/CFS symptom of post exertional malaise in later criteria. Baranuik shocked the audience when he said that Gulf War Illness – a major focus of his research – affects 25-32% of those deployed. Many had been exposed to chemicals.

    Baraniuk’s current ME/CFS study uses an MRI brain scan before and after a submaximal exercise test and early results from this unfinished study show changes in brain blood flow, especially after a cognitive test. Patients also show greater activation of the sympathetic ‘flight or fight’ nervous system than controls, and half of patients had postural tachycardia – a racing heart when they stand up, which may be linked to reduced blood flow.


    Big Data Approach: Severely Ill ME Patient Cohort - Professor Ron Davis

    Invest in ME had saved the best til last: “Davis delivered a mind-blowing presentation that drew the day’s longest round of applause by far.”

    Most people know that Davis is motivated by finding effective treatment for his son who’s very severely-affected. Davis was part of the IOM panel reviewing 9,000 publications and he said he found little useful biomarker data so decided to collect his own, teaming up with the Open Medicine Foundation to raise funds for a small but intense study. The study costs $70,000 a patient, even with many companies providing their services at greatly reduced because of the esteem in which they hold Davis (several are run by former students).

    While the study is small, with only 25 patients, Davis said focusing on the severely-affected who have a ‘larger molecular signal’, together with looking at many potential biomarkers simultaneously, increases the odds of finding biomarkers. Any promising biomarkers will be validated in larger groups of patients.

    Davis has some results in already, and the early findings are dramatic: they are….

    … well, you’ll just have to read Mark’s account to find out. It’s well worth it.

    Mark wrapped up his excellent account with personal reflections on the conference: he’s excited that things seem to be coming together at last in ME/CFS research.



    There are shorter, but less detailed write-ups from Dr Charles Shepherd of the ME Association, and Dr Rosamund Vallings for Invest in ME itself. Buy the Invest in ME conference DVD.
     
    Last edited: Jun 29, 2016
  7. Mark

    Mark Former CEO

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    Thanks for setting that up Simon. I've now added an index ('conference agenda') to the top of the article; hopefully that will make it easier for people to navigate.
     
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  8. Gingergrrl

    Gingergrrl Senior Member

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    Thank you @Mark for the great summary and am especially interested in the work being done at the Charite with trying to reduce autoantibodies with plasmapheresis, IVIG and RTX. I wish something like this experiment was being done in the US!
     
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  9. Jill

    Jill Senior Member

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    Thank you Mark for a great write up. I can only imagine how difficult it is to summarise technical stuff on such wide topics . You do it brilliantly, with an ME brain it must be so so hard. Thank you again. I love your reports.
     
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  10. Groggy Doggy

    Groggy Doggy Senior Member

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    Did you see Staines?
    "Staines said his group believe that ion channel receptor function, and calcium signalling problems, could be causing ME/CFS"
     
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  11. Gingergrrl

    Gingergrrl Senior Member

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    Hi GD, I am not certain if I'd read that exact link by Staines but it is possible b/c everyone on PR has been incredible with sending me links on this topic (and you've sent me some really amazing stuff- thank you so much! :hug:) I just bookmarked the post and also sent the link to myself.

    I truly believe that this is my core issue (calcium channelopathy) and if this turns out to be one of the sub-types of ME/CFS, then I am certain that this is the illness that I have. I wish I could fast-forward the science by about 10-20 years b/c at present many docs still feel that even with a positive ANA titer, calcium channel auto-antibodies, abnormal EMG, etc, that everything is "normal" or a "technical error" or other BS since I do not fit into the "lupus" box (or that of any other known autoimmune disease) in 2016 as if having POTS, MCAS and all these other issues are just random.

    But thank God my main doc, MCAS doc and new neuro all "think outside of the box" and got me approved for IVIG which I will start as soon as we can get it arranged. I am going to try to follow as closely as I can to the treatments in Dr. Scheibenbogen's study on my own and hoping it will give me some improvements.

    Will of course post about in the appropriate thread (and will not take this one off topic :D) but hoping everyone reads the portions of Mark's phenomenal summary that include the work being done at the Charite and the link you included to Staines's group. This stuff all makes me really hopeful that at least there is something that I can try with a fairly decent chance of being in the right sub-group for it.

    Thanks @Groggy Doggy
     
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  12. Simon

    Simon

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    I've already posted a summary of @Mark's long piece in an earlier post, and it's now on #MEAction:

    2016 Invest in ME Conference write-up on PR | #MEAction

    There are links in my summary piece that go direct to the releant section of Mark's full article, eg Ron Davis's talk.
    Big Data Approach: Severely Ill ME Patient Cohort

    Feel free to share the #MEAction article if you think it will help take the IiME conference to a wider audience :)

    [btw, Mark has also added an index at the start of his article so that you can again go direct to the different speaker's talks]
     
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  13. Sasha

    Sasha Fine, thank you

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    https://www.facebook.com/groups/580...0153802382167507&comment_tracking={"tn":"R0"}

    Can't wait! Next couple of weeks, then...
     
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  14. Sasha

    Sasha Fine, thank you

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    IiME just posted on FB that deliveries of the DVD will start at the end of the week. :woot:
     
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  15. wastwater

    wastwater Senior Member

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    Must get this years dvd,I'm usually in for the early bird a bit late for that.
    Interested in the microRNA whatever that is.
    Interested in CLL region at 13q14 which is where I tracked down my genetic focus to with riegers

    Buy it and make notes its very good,lasts about 8 hours in total.(works on a playstation 3)
    Mentions B cells the gut,calcium and metabolic pathways.
    Was interested to see serotonin and dopamine mentioned as you would expect as a way of shutting down function,these pathways seem very resistant to restarting
    Hsa-miR223-3p and hsa-miRNA-145-5p are they tumour suppressors
     
    Last edited: Sep 18, 2016
  16. wastwater

    wastwater Senior Member

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    Are professor oltra potential bio markers involved in tumour surpression?yes
     
    Last edited: Sep 19, 2016
  17. wastwater

    wastwater Senior Member

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    Having an oncovirus like EBV and missing tumour surpressor pathways sounds like bad synergy to me,maybe rituximab helps knock back any advancement of cancer formation
    Found something on 13q14 and B cells in leukemia https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778015/
    It mentions nematode worms too
     
    Last edited: Oct 27, 2016

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