Severe ME Day of Understanding and Remembrance: Aug. 8, 2017
Determined to paper the Internet with articles about ME, Jody Smith brings some additional focus to Severe Myalgic Encephalomyelitis Day of Understanding and Remembrance on Aug. 8, 2017 ...
Discuss the article on the Forums.

#OMFScienceWednesdays-Olav Mella talks autoimmunity and metabolism in ME/CFS

Discussion in 'General ME/CFS News' started by Ben H, Feb 14, 2018.

  1. Ben H

    Ben H OMF Correspondent

    Messages:
    803
    Likes:
    9,137
    U.K.
    Hi guys,

    It’s #OMFScienceWednesday! Today we share a video lecture by OMF Scientific Advisory Board member Dr. Olav Mella of the University of Bergen, Norway. In this lecture, Dr. Mella talks about the evidence for autoimmunity and metabolic disturbances in ME/CFS, and what such findings may mean for treatments. The lecture is in Norwegian but there are English subtitles available from the Closed Captions menu.

    Dr. Mella made the following points:
    Autoimmunity: It is clear that the immune system is involved in ME/CFS pathology, and he noted that while there is evidence for autoimmunity, ME/CFS does not behave like a ‘classical’ autoimmune disease;

    Genetics: Evidence for genetic predisposition to ME/CFS has been presented in many studies, and his team is currently studying families to understand this better;

    Cytokines: He believes that the many aberrations observed in cytokines – signalling molecules that can indicate inflammation – may reflect an underlying process involved in ME/CFS, but are unlikely to be the cause or hold the answers;

    Rituximab: Dr. Mella’s team has been exploring rituximab as a possible treatment, because of the evidence that B cells are overactive in ME/CFS – depleting them with rituximab could have beneficial effects for patients. His most recent clinical trial with rituximab did not show significant improvements in the patient group he studied. He believes physicians should be cautious about recommending rituximab treatment, but he also believes there is a subgroup of patients in which rituximab would be effective. The challenge is that we have no marker for identifying these patients;

    Cyclophosphamide: Dr. Mella’s most recent clinical trial with cyclophosphamide, which causes a more general immunosuppression, showed more promising preliminary results than that with rituximab. However, patients tolerate it less well – it causes nausea.

    For more details, watch the video / read the transcript on YouTube:




    Thanks guys,


    B

    @Janet Dafoe (Rose49) @AshleyHalcyoneH
     
  2. Diwi9

    Diwi9 Senior Member

    Messages:
    687
    Likes:
    2,447
    USA
    Thank you for your summary, @Ben H!
     
    echobravo, Gemini, Ruthie24 and 2 others like this.
  3. Ben H

    Ben H OMF Correspondent

    Messages:
    803
    Likes:
    9,137
    U.K.
    I cannot take credit, I am simply the inbetween trying to keep all up to date :)

    The hard work is done by Raeka Aiyar, Janet, Ron etc.


    B
     
    echobravo, Neunistiva, Gemini and 8 others like this.
  4. Diwi9

    Diwi9 Senior Member

    Messages:
    687
    Likes:
    2,447
    USA
    Anybody out there know just how many research groups are working on the genetic component? I know the Lights in Utah (any updates from them?), OMF, and now the Bergen Team. Wasn't there also a group at University of Arizona?

    Are there teams in Canada and the UK focussing on genetics?
     
    jpcv likes this.
  5. Gingergrrl

    Gingergrrl Senior Member

    Messages:
    10,216
    Likes:
    29,225
    USA
    Hi @Ben H, I bolded part of your quote above and have a question in case you or anyone knows the answer (and I am unable to watch the video at this time as much as I wish I could)!

    Did Dr. Mella say if he views the sub-group of Rituximab responders to have ME/CFS or to have a similar but different B-cell/autoantibody driven illness? Also, did he ever say if he felt that auto-antibodies to the anti-muscarinic or beta-adrenergic receptors, the positive ANA, or the anti-thyroid autoantibodies could be identified in the responders (like in Fluge & Mella's original journal article before we knew the study results)?

    Thanks in advance!
     
  6. Wonkmonk

    Wonkmonk Senior Member

    Messages:
    325
    Likes:
    496
    Germany
    If I get it right, he says no better results than placebo and not no results at all. But maybe from a scientific perspective that's no difference...
     
  7. Gingergrrl

    Gingergrrl Senior Member

    Messages:
    10,216
    Likes:
    29,225
    USA
    I don't know the answer from a scientific perspective, and I do not remember the real numbers, but if 100 people tried Rituximab and even five got better, I would want to study those five and know why. But that is just me ;)
     
  8. Wonkmonk

    Wonkmonk Senior Member

    Messages:
    325
    Likes:
    496
    Germany
    If you mean in this lecture, he addressed none of these issues. Rituximab was actually discussed very quickly, just 2-3 minutes. He said in their last trial it was no more effective than placebo, but he thinks it may work in a subgroup of patients and they are now working on identifying those patients. Oh well, and he said don't try it outside of scientific trials ;)
     
    Gingergrrl likes this.
  9. Wonkmonk

    Wonkmonk Senior Member

    Messages:
    325
    Likes:
    496
    Germany
    Absolutely, but a mystery of the first successful Rituximab trials was that there was no pattern whatsoever regarding who responded and who didn't. Age, gender, type of onset, own or family autoimmunity history, length of illness etc. ... none of that helped in identifying a specific subgroup of responders.

    And if the number of responders is low in the first place and you can't find any evidence for your theory why they responded (F/M think it's an autoimmune disease), then of course people get sceptical if the effect is real or really in fact a placebo effect or spontaneous recovery.

    It's very unfortunate that Kolibri, OMI and others who use RTX don't share much information on how many responders they have. The fact that they are continuing with RTX despite the negative results of F/M suggest that they are having some success with that kind of treatment.

    But if they do, why don't they share their results with the scientific and patient community?
     
    Gingergrrl likes this.
  10. Gingergrrl

    Gingergrrl Senior Member

    Messages:
    10,216
    Likes:
    29,225
    USA
    Thank you and I was just curious.

    I guess I am a rebel :cool:... although I am doing it for autoimmunity and not for ME/CFS.

    Did Dr. Mella say that F/M still view ME/CFS as an autoimmune disease in spite of the negative results from the Ritux trial?

    I know there has been success from both OMI and Kolibri b/c I have been in contact with patients from both places. But I have no way of knowing if the responders really have ME/CFS or an unknown autoimmune disease since no one really seems to know at this point in time.

    Mine is prescribed by my local MCAS doctor, in collaboration w/my main doctor who used to be at OMI but now in his own practice. My MCAS doctor was so impressed (shocked really) by my improvements from high dose IVIG that he actually read the materials I brought him re: Ritux and spoke to my main doctor on phone and felt I had a good chance of being a responder and that it was worth trying. But I never had an ME/CFS diagnosis given by my MCAS doc. He has a very long list of diagnoses for me including MCAS, POTS, Dysautonomia, Hashimoto's Disease, Multiple other auto-antibodies, pulmonary restriction (from prior PFT tests), etc.

    I really don't know and my guess (re: OMI, not Kolibri) is that they are so short-staffed with such minimal time/funding that they are focused on patient care.
     
  11. Diwi9

    Diwi9 Senior Member

    Messages:
    687
    Likes:
    2,447
    USA
    This is a good question and it seems like Mella was bending away from calling it autoimmune and rather saying it has characteristics of autoimmunity. He is convinced the immune system is dysfunctional and that in some, autoimmunity appears to develop...as best as I'm able to interpret.

    FWIW - I don't think you're placebo...medical science just doesn't understand you...so in that respect you're part of our ME/CFS club too.
     
    Ruthie24 and Gingergrrl like this.
  12. Gingergrrl

    Gingergrrl Senior Member

    Messages:
    10,216
    Likes:
    29,225
    USA
    Thanks and I know for sure that I am not placebo either (but don't know what I am :bang-head:)

    Even among the zebras, I am the freak LOL. Sorry, did not mean to side-track the thread, I am just so curious to understand Rituximab better. Most of my doctors now think I have "Autoimmune Dysautonomia" which doesn't have a name YET.
     
    echobravo and Diwi9 like this.
  13. Diwi9

    Diwi9 Senior Member

    Messages:
    687
    Likes:
    2,447
    USA
    I've just had additional autoimmune testing performed. My doctor thinks I'm starting to develop it. My ME/CFS is improved from last year, but my POTS is worse. Interesting, Mella stated that 15% of ME/CFS patients have POTS, I thought it was much higher.

    ETA: He also said that people with ME/CFS tend to have families with autoimmunity. MS and autism runs in my large family.
     
    echobravo and Gingergrrl like this.
  14. Gingergrrl

    Gingergrrl Senior Member

    Messages:
    10,216
    Likes:
    29,225
    USA
    What autoimmune testing did you have?
     
  15. Diwi9

    Diwi9 Senior Member

    Messages:
    687
    Likes:
    2,447
    USA
    Gingergrrl likes this.
  16. Gingergrrl

    Gingergrrl Senior Member

    Messages:
    10,216
    Likes:
    29,225
    USA
    @Diwi9 I can't tell from that link which autoantibodies are being tested and think I am missing something!
     
  17. Diwi9

    Diwi9 Senior Member

    Messages:
    687
    Likes:
    2,447
    USA
    Gingergrrl likes this.
  18. Wonkmonk

    Wonkmonk Senior Member

    Messages:
    325
    Likes:
    496
    Germany
    I don't know for sure, but it appears to me that they are stepping away from that idea to some extent. In their 2015 paper, they discussed that the response pattern actually doesn't suggest that reduction in autoantibodies due to B-cell depletion can be the entire story. Recovery occurs too late and relapse after recovery too fast compared to response patterns to RTX use in known autoimmune diseases like psoriasis and rheumatoid arthritis.

    So I think they still believe the subset of CFS patients who respond to RTX have an immunological defect, but not necessarily a typical autoimmune disease. Even in their very first paper, they didn't say CFS is an autoimmune disease, but said it might be "a variant of an autoimmune disease." (for me that's a difference, but maybe for physicians/scientists, it's the same - I don't know)

    In their papers, they also noted and discussed the fact that most of their patients did not have any known autoimmune disease and 60% even didn't have any known autoimmunity in their families.

    Interestingly, they have always rejected and as far as I know continue to reject (at least until their 2015 paper) the herpes virus hypothesis or generally the infection hypothesis. If it was EBV, response should occur much more quickly, because B-cells - EBV's main reservoir - are destroyed and if it's another virus that is not located inside the B-cells, there should be no response at all or even a deterioration, so that hypothesis is as far as I know still rejected.

    In one lecture which I linked to elsewhere, Dr Fluge was also sceptical of Dr Naviaux's hypothesis that CFS is a dysfunctional metabolic state akin to a state known as dauer in nematods. He said he thinks it's immunological, maybe caused by an antibody (I checked, he explicitly said "antibody" and not "autoantibody").
     
    Gingergrrl and Diwi9 like this.
  19. Gingergrrl

    Gingergrrl Senior Member

    Messages:
    10,216
    Likes:
    29,225
    USA
    Thanks and that looks extremely thorough if they are testing all of those autoantibodies and then further testing on the ones that are positive. I was not tested for all of those but on a much smaller paraneoplastic panel from Mayo, I was positive for VGCC N-type and GAD65.
     
  20. Diwi9

    Diwi9 Senior Member

    Messages:
    687
    Likes:
    2,447
    USA
    My understanding is that this a "new" panel provided by Quest.
     
    Gingergrrl likes this.

See more popular forum discussions.

Share This Page