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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. Ember

    Ember Senior Member

    A reproducible phenomenon will serve to reduce the stigma of ME too, a crippling stigma for a disabled community that, as you say, “has to rely on the man and woman in the street to be sympathetic.” Lewellyn King probably sums up the situation best for us in his article, “Hidden in Plain Sight.”

    The Arthritis and Rheumatism Council strategy of encouraging academic appointments sounds brilliant!
  2. currer

    currer Senior Member

    Hi Dr Edwards,

    My consultant Professor Pinching had clinical experience of using this drug in his ME/CFS clinic at St Bartholomews and in Cornwall over thirty years. He found that it improved half of his ME patients. Because of this he wanted to get funding for a randomised controlled trial for this drug but that was not forthcoming I'm afraid and he was unable to take his interest further.
    Unfortunately for us, this good doctor, who actively looked for drugs that gave his ME patients symptomatic relief, and as an immunologist, was interested in his patients' symptoms, and what this might reveal about the underlying pathology of this disease,has now retired.
    His care and respect for this patient group cannot be replaced. He worked in this field for over thirty years.

    Immunovir shifts the immune system from a TH1 to a TH2 balance and this is an abnormality that is recognised to exist in ME, so a drug that acts on this is likely to have some therapeutic effect.
    If this is a rationale you are not impressed with, remember it is only a theoretical rationale and the actual effect the drug is having may in reality be quite different. But if experience shows that something works, this is the gold standard and tells us something we ought to look at.

    Surely if a longstanding clinical experience shows that a drug is useful, this is worth investigation?

    It concerns me that the historic lack of research interest in ME/CFS has meant that promising research leads are not being followed up and useful clinical experience is being lost.
    This is very worrying.

    Professor Pinching worked in Britain, in the NHS. I am sure that you could contact him, even though he has now retired. As I said, Dr Fluge told me how helpful he was when they were designing the first Rituximab study and he had already retired then.

    On another point, after my initial illness I worked for our local ME support group, and over the next thirty years I noticed that ME seemed to be moving from affecting adults to children, in other words it was moving into a younger age group. Initially children with ME did not seem to exist. My GP also said to me recently that she had noticed that increasingly she was diagnosing girls at puberty.

    It worries me that these pointers about this disease are getting lost because the drive to do the research was not there historically and all we are left with now are anecdotal experiences.

    Thanks for coming here Dr Edwards and for taking the time to talk to us.

    I am glad to see that cornwall has put up the info sheet about immunovir as I do not have a working scanner.
    Cornwall, my experience with immunovir mirrors yours, that it had an effect immediately... this is why the theoretical rationale may not actually be what is going on to cause improvement.

    I took this sheet to my GP and she agreed to prescribe immunovir again.

    Because of this I have had a year of very good health, and I am angry that, like you, I was refused a drug that could help me by other doctors and had to suffer poor health unnecessarily.
    So take this sheet to a GP and they may feel reassured by what they read and able to take on the prescribing responsibility for this on the NHS.
    I had to pay for the drug though, and 160 tabs cost about £80
    MeSci and Sasha like this.
  3. currer

    currer Senior Member

    Another point that occurs to me is that my gut symptoms (bloating, etc) disappeared on the immunovir.
    I would hate to see research interest in this useful drug disappear.

    I hope we can start a fresh thread on immunovir so that we can discuss how this drug has helped us (or otherwise)
    I don't want to get this thread off topic.
    I do think that the immune effects of immunovir helped my gut problems, because since stopping this drug, the gut symptoms have returned - and I can remember now how miserable they were.
    This is consistent with the immunovir enabling the immune system to work more normally and to supress bacteria and fungi in the gut - especially as the tablets are swallowed.
    I have heard that the gut is immunologically an active organ so the immune changes in ME could well lead to gut problems..
  4. lansbergen

    lansbergen Senior Member

    I thought it reduces Th2 dominance.
  5. Heart Face

    Heart Face

    Then we want a name for what we think is a specific disease - or several. I have sympathy with the suggestion, not popular with all, that myalgic encephalopathy is a much better name than myalgic encephalomyelitis. I doubt that most people have true 'itis' of either brain or cord. But it does seem that the brain is not working properly. You want precision without overstatement. But we would want to link that to various pathogenic mechanisms. So maybe when the next slice of research has got sorted we might have BME and NKME for B cell related and NK cell related myalgic encephalopathies.

    Jonathan Edwards your comments about have worried some members of the ME community. Are you aware of Byron Hyde and Ian Lipkin's work? If you are can you please explain why you "doubt that most people have true "itis" of either brain or spinal cord?"
  6. Legendrew



    Speaking personally, i'd be very glad if there was no observable and measurable damage - especially if there is no itis!
  7. Sasha

    Sasha Fine, thank you

    Jonathan Edwards - I've just been reading this:

    on the relationship between diet and autoimmune disease. In the absence of medical treatment, a lot of us have tried all sorts of diets to improve our ME because diet is something we have access to. I've been reading lately about enormous improvements in various autoimmune diseases via diet claimed by some clinicians (e.g. Dr Susan Blum) and about the rise in autoimmune and other diseases being linked to a Westernised diet (e.g. Dr Colin Campbell).

    According to Cort's blog post, which is a general discussion of the role of diet and the gut in autoimmune disease: "Researchers are beginning to identify specific gut bacteria that may predispose patients to rheumatoid arthritis. They can turn RA free mice into RA mice simply by inserting bacteria in their guts."

    I'm wondering how this links in with the theory of B cells attacking cells through a process of random trial-and-error selection of cells.

    Also, what do you think about the idea in general that diet might be a cause of RA and other autoimmune diseases? And about diet as a treatment?
  8. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Dear Currer,

    Yes, Tony Pinching was in the year above me at medical school. He is a nice guy and a very good doctor.

    I do not want to upset anyone, but I am being a bit blunt here because I think it might help get focused. This is a great discussion, but to turn it into results I think we need to go for the main chance, not runners up. My reading of Tony's account is that he thought Immunovir helped a bit for maybe a third to half of people but not often long term. We used to have drugs like that for RA (and double blind trials to show they were a bit helpful) but I think we should be thinking at a new level. To me a drug is only really worth pushing at if it can make at least a quarter of people completely better and give a major benefit in half. If Tony had thought Immunovir was that good, why did he not do what I did - set up the trial with no funding, give the drugs personally and sit by the bedside taking blood pressure checks myself and pay for the drug myself out of my bank account? I suspect he did not actually think it was a game changer.

    Maybe Immunovir does work for some but 'clinical experience' is notoriously unreliable. I certainly would not trust mine as scientific evidence. TH1-TH2 balance was a fashionable idea in the 1990s but it was only really relevant to experiments in mice as far as I could see. I have always treated that sort of buzzword idea with scepticism. RA was supposed to be the classic 'TH1 disease' until it turned out to be antibody driven after all - if anything TH2 but the functional distinction was a misconception anyway. (You are probably right that you got better for another reason.) We need something a bit more down to earth and tied to evidence in human disease. We also want drugs whose action we understand absolutely - like rituximab, which removes B cells. Then we can work out how the disease works at the same time as getting it better. It may be worth someone doing an Immunovir trial if it helps a bit and is safe but it wouldn't have been that difficult for ME physicians to do over the last 20 years. Blaming things on lack of interest doesn't get the dinner cooked, even if I agree there may be lack of interest - bigtime![/quote]
    melamine, Sasha, NK17 and 5 others like this.
  9. Forbin

    Forbin Senior Member

    Re: Encephalitis

    In 2005, James Baraniuk et al. published an article in BMC Neurology titled:

    A Chronic Fatigue Syndrome Related Proteome In Human Cerebrospinal Fluid

    In 2010, Dr. Anthony Komaroff characterized these findings as demonstrating "a low-grade inflammation going on in the brain."

    [The quote is at 3:48]
  10. Heart Face

    Heart Face


    Well, for you maybe, but for those that believe that this is the defining feature of ME, probably not so. I've read comments that this is akin to wessley's theories. It's not good and I think please if Prof. Edwards could address what he actually meant by that comment, it will help us understand where he is coming from?
  11. Heart Face

    Heart Face

  12. Heart Face

    Heart Face

    "....An example would be when one feels intense nausea looking at rich delicious food when one has an acute viral illness
    . It is not that one has become sensitive to that food especially but that one’s brain has become sensitive to almost everything. My suspicion is that the sense of constantly being afflicted by viruses may be part of the same thing. I agree that it is not going to be as simple as that but I think it is worth considering."

    This is also concerning people.
  13. Marco

    Marco Grrrrrrr!

    Near Cognac, France

    Hi Gemini

    The paper below from Vernon and Reeves (CDC) summarises autoantibody findings in ME/CFS to that date (2005) including one study that failed to replicate Tan's findings (Cleare, Wessely etc) :

    Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome

    It may be of some interest that Vernon and Reeves did find some evidence of autoantibodies in young patients (to ssDNA - associated with both viral and bacterial infection) and in long duration patients (MAP2 where autoantibodoes have been demonstrated in patients with neuropsychiatric systemic lupus erythematosus).

    They conclude that certain non-common autoantibodies may be elevated in sub-sets of ME/CFS patients :

    Any papers citing this one (Vernon, Reeves) have done so for the purposes of discussion only - not to replicate or further explore autoantibodies in ME/CFS. Interestingly Tan has gone on to look at autoantibodies in cancer and refers back to the ME/CFS findings.
  14. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Thanks, I could not find anything under Lipkin or Hyde about tissue changes in ME in the PubMed catalogue of medical literature. I would be interested to know what you are referring to and to look at it.

    My reason for doubting true inflammation (-itis) in most cases is that inflammation in the brain and spinal cord produces what are known as localising neurological signs - like paralysis or loss of vision. You do not need a lot of inflammation to produce a fairly major defect in function. The clinical criteria for ME do not include signs of this sort so I presume they are not common. What we learnt in rheumatology is that quite a lot of serious diseases we thought were 'inflammatory' are not really about inflammation at all. Scleroderma and osteoarthritis might be examples. That is why it is an error to think that just because the blood tests called 'inflammatory markers' are normal, nothing is wrong - there may still be something very wrong. I am not doubting for a moment that there is something wrong in the brain in ME but I think inflammation is an old-fashioned term that is probably misleading here - as for scleroderma.

    Lots of diseases have inappropriate names and it does not matter. The danger I see in talking about myalgic encephalomyelitis is that it can be seen to overstate the case - and I suspect that is a major factor in the lack of interest we have been discussing. Quite simply, because doctors doubt the -itis they make the mistake of doubting the existence of the disease. Politically, it is the ME community shooting itself in the foot. Doctors will say - so why is the CRP normal and the MRI scan clear? (Dr Staines has I think found reduced bloodflow, which would be the opposite of inflammation.) The way to win a scientific case is to stick to the hard published data and always err on the side of understatement. What I find there is sympathy for is the case that despite not being able to find any evidence of overt inflammation people with ME are still in deep trouble from a physical disease. There is a real problem there and we need a more modern, more sophisticated approach to understanding it.
    aimossy, vli, currer and 7 others like this.
  15. Legendrew



    Do you remember which paper that was in? Sounds very interesting.
  16. Marco

    Marco Grrrrrrr!

    Near Cognac, France

    Prof Edwards

    You wrote this in response to Legendrew's query about finding a 'consistent and measurable abnormality'.

    This may not be directly relevant to autoimmunity per se (or it may be - who knows?) but there are an increasing number of published papers (including from Julia Newton's team) reporting current autonomic dysfunction in varying but pretty high proportions of ME/CFS patients.

    I appreciate that autonomic dysfunction is far from specific but may provide some clues to the underlying problem - but - it can be a major contributor to the illness burden (POTS, tachycardia, gastrointestinal problems, exercise intolerance etc) and is treatable on an individual basis once testing confirms which arm (s) of the ANS are dysfunctional.

    Given these ME/CFS research findings, the fact that autonomic dysfunction is treatable and the currently unknown etiology of ME/CFS (and indications from diabetic autonomic neuropathy that autonomic dysfunction if untreated can result in neuropathy), I wonder what you, having been a practicing clinician, think of this recommendation (made in the context of diabetic neuropathy but not intended to apply to that condition solely) :
  17. Heart Face

    Heart Face



    The Terminology of ME & CFS By Professor Malcolm Hooper

    introduced in the UK in 1956 by a former Chief Medical Officer
    (Sir Donald Acheson) and not by Dr Melvin Ramsay as is
    sometimes claimed. The word "benign" was used because it
    was thought at the time that the disorder was not fatal (as
    poliomyelitis could be, with which it had some similarity), but it
    was quickly realised by clinicians that ME was not a "benign"
    condition, as it has such high morbidity (i.e. such a lot of suffering
    and ill-health), so by 1988 clinicians had stopped using the word
    "benign" and referred to it as ME, the first to do so being Dr
    Ramsay. However, the ICD still uses the term "benign" in its

    MYO relates to muscle
    MYOSITIS = inflammation of muscle

    MYALGIA = pain in muscles (pain that is called "myalgic")

    MYOPATHY = any disease or disorder of muscle

    MYEL (or MYELO) relates to the spinal cord (the main nerve in
    the body)

    MYELITIS = inflammation of the spinal cord (NB. Not to be
    confused with the other meaning of myelitis, which =
    inflammation of the bone marrow, as in osteomyelitis)

    MYELIN SHEATH = a layer of fatty white material that surrounds
    and insulates nerve fibres

    DEMYELINATION = the loss of this protective insulation round
    nerve fibres (as seen in multiple sclerosis and sometimes also
    in ME)

    ENCEPHALON = the brain

    ENCEPHALO = relating to the brain

    "ITIS" on the end of a word = inflammation (eg. hepatitis =
    inflammation of the liver)

    So, ENCEPHALOMYELITIS = inflammation of the brain and
    spinal cord

    non-fatal disorder (inflammation) of the brain and spinal cord,
    with pain in the muscles

    ENCEPHALOPATHY = any non-inflammatory disorder affecting
    the brain

    Despite the claims of some psychiatrists, IT IS NOT TRUE THAT
    : there is, but these psychiatrists
    ignore or deny that evidence. For example:
    1988 In conjunction with the University of Pittsburgh, the US
    NIAID held a large research workshop called "Consideration of
    the Design Studies of Chronic Fatigue Syndrome". There were
    participants from the Centres for Disease Control and from the
    National Institutes of Health. One of the presentations was by Dr
    Sandra Daugherty, who reported that MRI scans on patients
    demonstrated abnormalities consistent with demyelination and
    cerebral oedema in 57% of patients studied. (It was at this
    conference that it was recommended that the term "CFIDS" be
    used instead of the term "CFS" on the basis of the immune
    dysfunction that had been observed in the disorder).
    1989 Detection of Viral-Related Sequences in CFS Patients
    using Polymerase Chain Reaction W.John Martin (Nightingale
    Research Foundation: 1989: 1-5
    1990 Chronic Fatigue Syndrome and the Psychiatrist SE
    Abbey, PE Garfinkel Canadian Journal of Psychiatry
    1992 A Chronic Illness Characterised by Fatigue, Neurologic
    and Immunologic Disorders, and Active Human Herpesvirus
    Type 6 Infection D Buchwald, PR Cheney, R Gallo, AL Komaroff
    et al Annals of Internal Medicine 992:116:2:103 This paper
    states "Magnetic resonance scans of the brain showed
    punctate, subcortical areas of high signal intensity consistent
    with oedema or demyelination in 78% of patients"
    1994 Detection of Intracranial Abnormalities in Patients with
    Chronic Fatigue Syndrome: Comparison of MR Imaging and
    SPECT. RB Schawrtz, BM Garada American Journal of
    Roentgenology 1994:162:935-941
    1995 Pathophysiology of a Central Cause of Post-Polio Fatigue
    Richard Bruno et al Annals of the New York Academy of
    Sciences 1995:753:257-275
    1997 A 56-year old woman with chronic fatigue syndrome
    Anthony J Komaroff JAMA 1997:278:14:1179-1184

    It is true that there is no evidence of inflammation of the brain or
    spinal cord in states of chronic fatigue or "tiredness."

    It is also true that neither the 1991 (Oxford) criteria nor the 1994
    (CDC) criteria select those with ME, as they both expressly
    include those with somatisation disorders and they expressly
    exclude those with any physical signs of disease (as is the case
    in ME), so by definition, patients with signs of neurological
    disease have been excluded from study.

    It is also true that Professor Simon Wessely and his colleagues
    use the terms "fatigue", "chronic fatigue", "the chronic fatigue
    syndrome (CFS)" and "myalgic encephalomyelitis (ME)" as
    synonymous. Such obfuscation has greatly hindered research,
    as pointed out in the 1994 Report of the National Task Force on
    Chronic Fatigue Syndrome (CFS), Post-Viral Fatigue Syndrome
    (PVFS) and Myalgic Encephalomyelitis (ME), published by
    Westcare, Bristol and supported by the UK Department of
    Health, which stated:

    "Chronic fatigue syndromes remain poorly understood. Progress
    in understanding them is hampered by:

    • the use by researchers of heterogeneous study groups

    • the use of study groups which have been selected using
    different definitions of CFS

    • the invalid comparisons of contradictory research findings
    stemming from the above".

    The Report names psychiatrists Dr Simon Wessely, Dr Peter
    White and Dr Michael Sharpe and acknowledged their help, but
    then makes the point that "people who gave their help are not
    necessarily in agreement with the opinions expressed" (page
    87). It was said to be because those psychiatrists strongly
    disagreed with the findings of the 1994 Westcare Report that in
    1996 they produced their own report (the Report of the Joint
    Royal Colleges on CFS (CR54), which was internationally
    recognised as being biased and seriously flawed).


    The WHO was founded in 1948.

    The International Classification of Diseases (ICD) comes in two
    volumes: Volume I is the Tabular List and is a list of codes plus
    the name of the condition which goes with that code. Volume II is
    the Code Index, which alphabetically lists all the phrases and
    names of conditions commonly used for a condition, together
    with the appropriate code.

    The Tabular List (Volume I) does not list
    everything which is in the Code Index (Volume II).

    Benign myalgic encephalomyelitis (ME) has been classified in
    the International Classification of Diseases (ICD) as a
    neurological disorder since 1969, when it was included in ICD-8
    at Volume I: code 323: page 158 and in Volume II (the Code
    Index) on page 173. (ICD-8 was approved in 1965 and
    published in 1969).

    Prior to 1969, the term benign myalgic encephalomyelitis (ME) did not appear
    in the ICD, but non-specific states of chronic fatigue
    were classified with neurasthenia under Mental and Behavioural Disorders.

    Benign myalgic encephalomyelitis (ME) was included in ICD-9
    (1975) and is listed in Volume II on page 182.

    The term "Chronic Fatigue Syndrome" was not introduced by
    Holmes et al until 1988 and therefore did not appear in the ICD
    until 1992, when it was listed as an alternative term for benign
    myalgic encephalomyelitis (ME). Another alternative term listed
    is Post-Viral Fatigue Syndrome.

    In ICD-10 (1992), benign myalgic encephalomyelitis (ME)
    continues to be listed under Disorders of the Nervous System at
    G93.3, with the term Syndrome, Fatigue, Chronic, as one of the
    descriptive terms for the disorder.

    By contrast, in ICD-10 (1992), neurasthenia and other
    non-specific syndromes of on-going or chronic "fatigue" are
    listed at section F48.0 (Volume I, page 351). Non-specific states
    of chronic fatigue are classified as Mental and Behavioural
    Disorders, subtitled "Other Neurotic Disorders".

    Note: benign myalgic encephalomyelitis (ME/CFS/PVFS) is
    expressly excluded by the WHO from this section.

    Note also that the WHO has confirmed in writing that "it is not
    permitted for the same condition to be classified to more than
    one rubric as this would mean that the individual categories and
    subcategories were no longer mutually exclusive".

    Therefore, ME/CFS cannot be known as or included with
    neurasthenia or with any mental or behavioural disorder.

    Professor Malcolm Hooper 010-Encephalopathy Hooper.htm
    irwinsturtle likes this.
  18. MeSci

    MeSci ME/CFS since 1995; activity level 6?

    Cornwall, UK
    Is oedema classified as inflammation?
  19. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Mice do not get RA, they get given 101 different sorts of arthritis that can look a bit like RA. I am sure some of these can be fired up by bacteria but that is a million miles away from human RA. If RA was triggered by bacteria there would be epidemics as there are for Reiter's syndrome, which IS triggered by bacteria. As far as I know there is no good evidence for diet being relevant except in coeliac disease. Sorry, but this story has been going for fifty years and when one looks at the studies they do not tell us anything as far asI can see. People with RA have been trying all sorts of diets for over a century and nobody has found any consistent response.
    aimossy, Sasha and Firestormm like this.
  20. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    NK17 likes this.

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