1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Join the National PR Campaign for ME: Power to the Patient (P2tP)
Have you had enough of all the neglect and abuse of ME/CFS patients? Gabby Klein says now is the time for a National PR Campaign for ME/CFS to impress a change. Join the Patient Revolution to restore power to ME patients ...
Discuss the article on the Forums.

Invest in ME/Prof Jonathan Edwards statement on UK Rituximab trial, 30 July

Discussion in 'General ME/CFS News' started by Sasha, Jul 30, 2013.

  1. Jill

    Jill

    Messages:
    51
    Likes:
    54
    Auckland, NZ
    Prof said : ' I am not sure it is such a big problem. Non-specificity in relation to 'disease' pigeonholes does not matter if the feature of interest indicates a sort of mechanism to which one can target a rational treatment. '

    Well said.
    Our problem is drs have been trying to desperately pigeon hole us with little success and terrible consequences for us in that we fall thru all the cracks. It seems that if we can't be pigeon holed we can't be treated, hence why we feel ignored etc. I wish more medics had your way of thinking!. But as you say above, medicine unfortunately has been commercialized and this doesn't help lateral thinkers gain traction. Not enough fishing expeditions and experimentation. When you think about it , it was only during desperate times of war that medicine made its biggest advances. When ANYTHING was tried with the hope it might work and there weren't "rules" etc.
     
    NK17, rosie26, aimossy and 1 other person like this.
  2. MeSci

    MeSci ME/CFS since 1995; activity level 6

    Messages:
    3,694
    Likes:
    4,396
    Cornwall, UK
    It's a common theme that people with ME tend to be extra-sensitive to a wide range of drugs. I find it useful at times, as it means I can use less, which is cheaper!

    @Jill, has your friend tried lower doses of diclofenac (generic name for Voltaren/Voltarol)?
     
  3. Firestormm

    Firestormm Guest

    Messages:
    5,824
    Likes:
    5,976
    Cornwall England
    @Jonathan Edwards

    Do you think we might see a protocol for the UK study pertaining to Rituximab/autoimmunity released before the end of 2013? I wondered if there was anything you could tell us about how its all going at UCL?

    Thanks
     
    rosie26, Bob and aimossy like this.
  4. Tuha

    Tuha Senior Member

    Messages:
    792
    Likes:
    929
    I would like to ask you what you think how far we are to beat autoimmune diseases. Did we already do a big progress in autoimmunity diseases? Are autoimmune diseases simmilar- so a major discovery in one autoimmune disease could also help other autoimmune diseases or are autoimmune diseases too different? I ask this because of ME perspective. With so few money for ME research I think we need a miracle or a help from the discoveries from other diseases which could bring us further.
    I hope my question is not stupid - I am economist :)
     
    rosie26 and aimossy like this.
  5. Jonathan Edwards

    Jonathan Edwards Board Member

    Messages:
    980
    Likes:
    4,724
    From my perspective everything is going according to plan at UCL, with various people having done sterling work in getting things started. The slowness of bureaucracy takes its toll but one has to learn to bear with that in this world it seems. It was decided to do a preliminary blood test study on patients who might be suitable for inclusion in a trial, with the hope that this would allow grouping of patients in a way that could make the trial much more informative. That study has been designed and agreed and has gone for administrative approval, to start as soon as approval is available and a research worker has been allocated to the project. A detailed protocol for a trial will then be selected from options that have been considered, in the light of the blood test study. I am afraid I cannot give a useful idea of how long things are going to take but the momentum is there to get on with things as fast as is practical.
     
    ukxmrv, Simon, Gemini and 10 others like this.
  6. Jonathan Edwards

    Jonathan Edwards Board Member

    Messages:
    980
    Likes:
    4,724
    Progress in autoimmune disease during my professional lifetime has been enormous. When I first started we had steroids and a few other drugs that did not work very well and were very toxic. We had very little idea how autoimmune processes worked. Now we have a range of drugs which can produce complete remission of symptoms for long periods in many of the autoimmune disorders. We also have a pretty good idea of what is going on. There are still major issues about making treatments safe and practical and trying to get permanent remissions but at least we have a good idea what we should be aiming to do. There are common principles to many autoimmune diseases - so that many of them respond to treatments like rituximab.

    The question is a very intelligent one. In fact almost all of the new drugs for autoimmunity were developed for completely different diseases - some of them turn out to work better in autoimmune disease than for what they were designed for! There was no money to develop rituximab for RA. I had to buy the stuff and try it out on my own. So the situation for ME need not be so different - it just needs people to be interested in trying and I think they are beginning to be.
     
    NK17, Gemini, Roy S and 8 others like this.
  7. Firestormm

    Firestormm Guest

    Messages:
    5,824
    Likes:
    5,976
    Cornwall England
    Thanks ever so much for the update. Are you able to expand on this blood test? What it is you are looking for perhaps? Totally understand if you can't of course.
     
    rosie26 and aimossy like this.
  8. Jonathan Edwards

    Jonathan Edwards Board Member

    Messages:
    980
    Likes:
    4,724
    I would prefer not to comment in more detail at this stage. I would normally be happy to describe my own work but I will not be the principal investigator for this work. My role has been to get a collaboration together. I should not be giving a running commentary on other people's efforts. There are also reasons for being cautious about making information available too soon. We may actually want the trial to start without the people treating the patients, or the patients, knowing what the detailed results of the preliminary study are. This may seem odd (some other member of the team or maybe a sealed brown envelope will know) but we need to try very hard to avoid anything that might flavour expectations of results because assessments of fatigue are subjective.
     
    NK17, ukxmrv, Simon and 7 others like this.
  9. froufox

    froufox Senior Member

    Messages:
    397
    Likes:
    65
    Apologies that I havent kept up with this thread for a few months, but just to add my 2 cents here....I went to a talk recently given by a nutritionist which was specifically about autoimmune illnesses and he discussed several cases of his all of whom responded/improved significantly to treatment which included addressing pathogens, leaky gut, liver detox issues and nutritional deficiencies. Some improved to the extent that they completely lost their original diagnosis, to the surprise of their consultants. Illnesses included RA, Sarcoidosis, Neuromyelitis Optica, MS, SLE.
     
    Last edited: Dec 1, 2013
    rosie26 likes this.
  10. Bob

    Bob

    Messages:
    8,570
    Likes:
    11,477
    South of England
    Drawing Prof Edwards' attention to the 11th IACFS/ME Biennial International Research and Clinical Conference, in case it piques your interest in any way...

    Especially this bit:

     
  11. Bob

    Bob

    Messages:
    8,570
    Likes:
    11,477
    South of England
    I thought Prof Edwards might be interested in this...

    I've also started a separate thread (click here.)


    The Study:
     
    rosie26 and MeSci like this.
  12. Kate_UK

    Kate_UK Senior Member

    Messages:
    232
    Likes:
    228
  13. Ember

    Ember Senior Member

    Messages:
    1,728
    Likes:
    1,781
    Keynote Speech at IIMEC9
     
  14. Jonathan Edwards

    Jonathan Edwards Board Member

    Messages:
    980
    Likes:
    4,724
    Thanks Bob for the pointer to the narcolepsy T cell study. I have been away for a bit and am catching up. I thought I would reply here as it is a general comment of wider relevance.

    What intrigues me is that this study provides very plausible evidence for a sort of autoreactivity that probably bears no relation to any of the well known autoimmune diseases. It is a sort of autoreactivity that has often been assumed to occur - T cell based and involving 'cross-reactivity' - but in practice virtually all other autoreactivity (autoimmunity) has only been demonstrated in terms of B cell responses (and no cross -reactivity). A relevant point is that cross-reactivity for B cells (antibody mediated) is not particularly likely to overlap with cross reactivity by T cells since B cells recognise the shape of a whole protein and T cells recognise chopped up peptides.

    So if this study can be confirmed this would not just be another autoimmune disease. It would be a completely new sort of disease. (And rituximab would probably have no effect, even if given before damage was done.)

    Very interesting.
     
    NK17, aimossy, MeSci and 3 others like this.
  15. Bob

    Bob

    Messages:
    8,570
    Likes:
    11,477
    South of England
    Hypothesising, do you think that T-cell mediated auto-reactivity, involving what you describe as cross-reactivity, could potentially be responsible for auto-immunity that is less localised (e.g. rheumatoid arthritis or asthma), but more generalised/systemic? Or am I barking up the wrong tree?

    BTW, Charles Shepherd, of the ME Association says: "There are some interesting causative, clinical and management overlaps between narcolepsy and ME/CFS."
     
    NK17 likes this.
  16. Jonathan Edwards

    Jonathan Edwards Board Member

    Messages:
    980
    Likes:
    4,724
    T cell mediated responses tend to be more local than antibody-mediated ones. T cells will only recognise antigens presented by cells so the reaction will only occur where cells have picked up and preented antigen locally. Antibody mediated responses can involve immune complexes in which the antigen is in the circulation, so the response can be almost anywhere there is blood supply. Antibodies do not tend to get into brain however, except in multiple sclerosis where somehow B cells get into the brain linings (meningeal spaces) or even into brain tissue itself. The more or less silent (non-inflammatory) death of hypocretin producing neurons in the absence of any other events elsewhere would fit very well with a local T cell attack.
     
  17. lansbergen

    lansbergen Senior Member

    Messages:
    1,099
    Likes:
    538
    I@ jonathan Edwards Would you call an innate reaction to a misfolded cellulair protein autoimmunity?
     
  18. Jonathan Edwards

    Jonathan Edwards Board Member

    Messages:
    980
    Likes:
    4,724
    No, I think the agreed definition of autoimmunity is an adaptive reaction - i.e. based on acquired mutations in B or T lymphocyte receptors. We all have innate reactions to misfolded self proteins in all cells - which allow the cell to destroy any protein molecules that for some reason have not folded normally.
     
    NK17, Valentijn and rosie26 like this.
  19. lansbergen

    lansbergen Senior Member

    Messages:
    1,099
    Likes:
    538
    Thank you
     
  20. Legendrew

    Legendrew Content team

    Messages:
    535
    Likes:
    692
    UK
    I'm sorry if this is dragging up an old point, I've only recently been going through this thread for the comments I have missed. The concept of 20+ autoantibodies being present within the entire potentially autoimmune based ME cohort is something that sounds very interesting and is something I doubt many people have ever considered.

    From my reading around the subject it seems clear that there is a definite 'neurological' dysfunction in ME patients and the most common term I see when reading articles around this subject are autonomic dysfunction (which, while an interesting topic is something of an overly broad term) and HPA axis dysfunction (hypothalamic-pituitary-adrenal axis). I admit that much of the discussion regarding this is somewhat beyond me (although I intend to read up on the subject at some point) however it seems an interesting concept, especially given that there could be thousands of unique targets within the hypothalamus and pituitary gland. I'll be interested to see whether the study investigating possible hypothalamus targeted antibodies comes up with anything.

    Such dysfunction could go some way to explain the vast array of symptoms patients experience and also the seemingly vast spectrum of morbidity between patients, with some completely bed bound while others are able to struggle on, working full-time. It could also explain why generic test such as blood counts, ESR and CRP are very often normal in patients despite high levels of disability.

    That aside, I do have a query regarding the rituximab trial. Are you also recording patients self reported symptoms alongside results from the pre-trial study? It would be interesting to see whether certain symptoms such as swollen lymph nodes, headaches, tremors etc are more or less frequent in a possible responding group - although I doubt this will prove a significant difference I would expect some symptoms to appear more frequently in those who respond. Acute/gradual onset could also have a huge difference although i'm certain these are things you've already considered. I was reading a paper recently exploring how cytokine fluctuations in Lupus appear to correlate to differing symptom complexes (http://www.ncbi.nlm.nih.gov/pubmed/8445045). It's interesting to see the variation that exists even within a fairly well defined disease such as lupus. If ME did truly have numerous different causative autoantibodies perhaps the degree of variation within ME would be even greater.
     
    Last edited: Jan 21, 2014
    NK17 and rosie26 like this.

See more popular forum discussions.

Share This Page