Phoenix Rising supports the Millions Missing global day of protest
Phoenix Rising is delighted to support the demands being made in the ME/CFS community’s first-ever global day of protest …
Discuss the article on the Forums.

Newcastle University experts in hunt for "smoking gun" of chronic fatigue syndrome ME

Discussion in 'General ME/CFS News' started by Cheesus, Nov 29, 2016.

  1. Cheesus

    Cheesus Senior Member

    Messages:
    1,229
    Likes:
    5,494
    UK
    http://www.thenorthernecho.co.uk/NE...ing_gun_quot__of_chronic_fatigue_syndrome_ME/

    Thank you to @charles shepherd for this. I assume one of the experts in question is Julia Newton?
     
    Woolie, actup, zzz and 24 others like this.
  2. Gijs

    Gijs Senior Member

    Messages:
    642
    Likes:
    1,296
    I don't believe in one simple bloodtest for a heterogeneous disorder. It doesn't match with the findings.
     
  3. Cheesus

    Cheesus Senior Member

    Messages:
    1,229
    Likes:
    5,494
    UK
    It might be that we have a common endpoint that is measurable in a single blood test. Even if there is nothing to find, a negative result would still be valuable. This research is definitely worth doing.
     
    Woolie, actup, erin and 7 others like this.
  4. Sasha

    Sasha Fine, thank you

    Messages:
    12,783
    Likes:
    34,198
    UK
    Is this the Make ME Better project, @charles shepherd? Has the £50,000 goal been reached?
     
    actup and Valentijn like this.
  5. worldbackwards

    worldbackwards A unique snowflake

    Messages:
    2,091
    Likes:
    10,358
    Earth
    Pretty sure it is. £30,000 up as far as I've seen, so not bad at all.
     
    actup and Sasha like this.
  6. charles shepherd

    charles shepherd Senior Member

    Messages:
    2,238
    Likes:
    16,190
    Invisible Woman likes this.
  7. charles shepherd

    charles shepherd Senior Member

    Messages:
    2,238
    Likes:
    16,190
    Yes, this press coverage follows on from a Press Release about our Xmas Appeal

    We have received almost £30,000 in donations in just two weeks - which is a pretty good response!

    CS
     
  8. Cheesus

    Cheesus Senior Member

    Messages:
    1,229
    Likes:
    5,494
    UK
    Just to be clear, the research has not actually been funded yet? The reason I ask is that I assumed it had and so I emailed my immunologist at the RVI in Newcastle this morning - the regional ME 'champion' - to ask if I could be included, and he said he hadn't heard of any research taking place at Newcastle. He is a colleague of Julia Newton so I was quite surprised by that.
     
  9. charles shepherd

    charles shepherd Senior Member

    Messages:
    2,238
    Likes:
    16,190
    The research has not yet started

    We are raising money to fund this research study through our Xmas Appeal

    This is the MEA website information from the launch of the appeal just over two weeks ago:

    http://www.meassociation.org.uk/201...hristmas-appeal-starts-today-9-november-2016/

    If you are a member of the MEA there is further information in the November issue of ME Essential magazine
     
    Sasha, Cheesus and Invisible Woman like this.
  10. Hip

    Hip Senior Member

    Messages:
    9,371
    Likes:
    14,736
    The "ATP Profiles" energy metabolism blood test used by Myhill, Booth and McLaren-Howard is able to almost perfectly distinguish ME/CFS patients from healthy controls.

    The graph below shows how the mitochondrial energy score (which is determined by the "ATP Profiles" test) neatly distinguishes between ME/CFS patients and health controls in nearly all cases:


    Mitochondrial Energy Score (Derived From the "ATP Profiles" Blood Test),
    Plotted Against the Disease Severity Level for Each ME/CFS Patient.
    Healthy Controls are Represented by the Black Dots.


    Figure 4a.png
    Figure 4a from Myhill, Booth and McLaren-Howard's 2009 Paper.​


    Now, the interesting thing about the "ATP Profiles" blood test is that the faults it finds in the energy metabolism of ME/CFS patients are different for every patient. If you were just to measure one area of energy metabolism, you would not get the above graph that neatly distinguishes ME/CFS patients from healthy controls, because even the severe ME/CFS patients were often found to be perfectly normal in some areas of their energy metabolism operation, but highly defective in other areas. So you have to take all areas into account when distinguishing patients from healthy controls.

    In other words, although all the patients had ME/CFS, there were different patient subsets identified, according to which particular areas of the energy metabolism were at fault in each patient. There was no one energy metabolism fault "signature" for ME/CFS patients, but rather a series of signatures. More info in this thread: Mitochondrial and Energy Metabolism Dysfunction in ME/CFS — Myhill, Booth and McLaren-Howard Papers



    I mention this because when trying to find a biomarker for ME/CFS via metabolomic analysis, it is quite possible that you will not find one single biomarker that neatly distinguishes ME/CFS patients from healthy controls; you may find different ME/CFS patient subsets, and will only be able to separate ME/CFS patients from healthy controls when you take all the subsets into account.

    In one ME/CFS patient subset, there may be a certain set of metabolic signatures present — call it set 1. But in a different ME/CFS patient subset, the set 1 metabolic signatures may be entirely absent, but in these patients you may instead find another set of metabolic signatures present — call it set 2. Thus if you were only testing ME/CFS patients using the set 1 signatures, you'd miss all the ME/CFS patients who have set 2 signatures.

    So I think this sort of thing needs to be borne in mind when searching for metabolomic signatures present in ME/CFS patients.
     
    Last edited: Nov 29, 2016
    Cohen2, actup, taniaaust1 and 10 others like this.
  11. Esther12

    Esther12 Senior Member

    Messages:
    8,449
    Likes:
    28,522
    We need independent replication. I've seen a number of people be critical of that 2009 paper from Myhill, Booth and McLaren-Howard. Wasn't MEA involved in some sort of replication attempt? Not sure if we have results from that yet.
     
  12. Mary

    Mary Senior Member

    Messages:
    2,745
    Likes:
    6,134
    Southern California
    @Hip - I had ATP testing done by Sarah Myhill 6-1/2 years ago and it showed marked deficiencies in ATP production. But I can't tell where I would be plotted on your graph.

    She did 6 different tests, and I'm assuming the one related to your graph is the one that has 3 parts: ATP Studies on Neutrophils, ADP to ATP conversion efficiency and ADP-ATP Translocator. My results were low on every variable but don't know how they fit into your graph.

    There is a number at the bottom of the page, 15/100, and I don't know what it means. There's another number at the bottom which is 0.11, and again it's not identified.

    Can you tell me if either of these two numbers identify where I would fit on your graph?

    Or if you needed all the variable figures (11 of them), I'd be happy to post them. Thanks for your help.
     
  13. Sidereal

    Sidereal Senior Member

    Messages:
    3,097
    Likes:
    17,174
    I find it odd we are being asked to donate money for a project for which no scientific detail has been provided.
     
  14. HowToEscape?

    HowToEscape? Senior Member

    Messages:
    468
    Likes:
    614
    Agreed. Why must the disease be obvious in blood? It could be a malfunction in x bodily process which does not leave obvious signs in blood. We're not looking for a virus, bacteria or foreign substance, though those may be present in addition to whatever knocked us out.

    Let me make an anology with zero knowledge of biology, thus very rough:
    Imagine you have an auto engine where the even # cylinders run rich, while the odd # run lean.
    Your diagnostic tools are examining the power output (exercise test) and a chemical analysis of the used engine oil. Everything reads about normal, though a close reading shows traces of unburned fuel in the engine oil and faint signs of overheating. Still, all is still broadly within the range of usual results.
    Dx: "No problem found."

    Then, the next time the engine approaches its full design load, the lean cylinders detonate, crack pistons and the engine from then on is crippled (it will be destroyed if running with a load is attempted).
     
    taniaaust1 likes this.
  15. Hip

    Hip Senior Member

    Messages:
    9,371
    Likes:
    14,736
    We do. But I brought up the Myhill et al paper not to discuss it so much, but as an example of the need to identify and take into account different ME/CFS patient subsets if you want to develop test that reliably distinguishes ME/CFS patients from healthy controls.

    Myhill et al would not have been able to distinguish ME/CFS patients from healthy controls if they had only focused on one area of energy metabolism; it required taking into account possible dysfunctions in several different areas. That is the point I am making, and it think it would apply to metabolomic studies as well.



    @Mary Why don't you repost you above post on the Myhill paper thread, and I'll try to answer your questions there. If you can take a picture of you test results page and post it, it may help.
     
    actup, taniaaust1, Mel9 and 1 other person like this.
  16. Esther12

    Esther12 Senior Member

    Messages:
    8,449
    Likes:
    28,522
    Without wanting to be rude about it, I'm a bit concerned this sort of thing just plays into the hands of the spin we see from Wessely and co. I don't see any good reason to to bring it up when 1) it's so much less important than getting to the truth and helping find genuinely effective treatments and 2) we know how harmful it has been for ME advocacy to be presented as being in some way 'anti-psych'.

    I realise it can be hard to do these sorts of things, particularly when the media seems so drawn to this 'psych vs bio' drama, and journalists will take the bits that interest them most, but this is an area where it's really worth trying to be extra careful imo.
     
  17. Hip

    Hip Senior Member

    Messages:
    9,371
    Likes:
    14,736
    That is the first time I have heard anyone suggest that the ME/CFS community should not be anti-BPS!

    Myself I don't think the substantial progress we have made in recent years, in making the BPS model of ME/CFS look like the farce it really is, would have occurred if the ME/CFS community were not fiercely ant-BPS.
     
    Last edited: Nov 29, 2016
    actup likes this.
  18. Mary

    Mary Senior Member

    Messages:
    2,745
    Likes:
    6,134
    Southern California
    Thanks, Hip, will do --
     
  19. worldbackwards

    worldbackwards A unique snowflake

    Messages:
    2,091
    Likes:
    10,358
    Earth
    I think Esther is saying that we'd do better just ignoring them and promoting our own ideas, rather than defining ourselves against them: there's a time and a place for that stuff.

    If we have indeed made so much progress, better not to bring them up.
     
    Last edited: Nov 29, 2016
  20. charles shepherd

    charles shepherd Senior Member

    Messages:
    2,238
    Likes:
    16,190
    The MEA Ramsay Research Fund is funding, or has been funding, four separate research studies into the role of mitochondrial dysfunction in ME/CFS and how it should be assessed - including the expensive commercial test that is being referred to

    MEA funded research into the commercial mitochondrial function test:

    http://www.meassociation.org.uk/201...-further-mitochondrial-research-20-july-2015/

    The main problem here is that this expensive commercial test has not been validated by other independent researchers - which is why it is not used (and is normally dismissed) by NHS doctors who specialise in muscle and mitochondrial disease

    The results from the research we have funded in Newcastle are now being analysed, along with some further laboratory work which has been done on this commercial test by two other independent researchers. The results will then be submitted for publication. Once the results have been published, the MEA will be making a further statement on this commercial test.

    In our present state of knowledge, there is insufficient evidence to conclude that any of these commercial mitochondrial function test results are a reliable indicator of muscle or mitochondrial involvement or function in ME/CFS

    And if mitochondrial function needs to be investigated, especially to rule out primary mitochondrial disease - which can be misdiagnosed as ME/CFS, then there are 'Gold Standard' NHS tests available (muscle biopsy, MRS etc)

    So this is NOT a test that we can currently recommend or endorse

    MEA funded studies into mitochondrial dysfunction:

    www.meassociation.org.uk/2016/03/me-association-to-fund-fourth-study-into-the-role-of-the-mitochondria-in-mecfs-10-march-2016/

    I would add that I have a deep personal interest in mitochondrial dysfunction having used my own skeletal muscle in the first research studies (which took place in the 1980s) to demonstrate evidence of mitochondrial dysfunction in ME/CFS.

    The first research, which I did with Professor George Radda et al at Oxford, and involved magneruc resonance spectroscopy, was published in The Lancet (abstract below).

    The second, which involved electron microscopy of mitochondria from biopsy specimens, was carried out by Professor Mina Behan et al in Glasgow (abstract below).

    Dr Charles Shepherd
    Hon Medical Adviser, MEA

    Abstract from Lancet paper:


    1984 Jun 23;1(8391):1367-9.
    Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. A 31P nuclear magnetic resonance study.
    Abstract
    A patient with prolonged post-viral exhaustion and excessive fatigue (CS) was examined by 31P nuclear magnetic resonance. During exercise, muscles of the forearm demonstrated abnormally early intracellular acidosis for the exercise performed. This was out of proportion to the associated changes in high-energy phosphates. This may represent excessive lactic acid formation resulting from a disorder of metabolic regulation. The metabolic abnormality in this patient could not have been demonstrated by traditional diagnostic techniques.

    Acta neuropathologica electron microscopy paper abstract:

    Behan, W.M.H., More, I.A.R. & Behan, P.O. Acta Neuropathol (1991) 83: 61. doi:10.1007/BF00

    Summary
    We have examined the muscle biopsies of 50 patients who had postviral fatigue syndrome (PFS) for from 1 to 17 years. We found mild to severe atrophy of type II fibres in 39 biopsies, with a mild to moderate excess of lipid. On ultrastructural examination, 35 of these specimens showed branching and fusion of mitochondrial cristae. Mitochondrial degeneration was obvious in 40 of the biopsies with swelling, vacuolation, myelin figures and secondary lysosomes. These abnormalities were in obvious contrast to control biopsies, where even mild changes were rarely detected. The findings described here provide the first evidence that PFS may be due to a mitochondrial disorder precipitated by a virus infection.
     
    taniaaust1, Rvanson, voner and 2 others like this.

See more popular forum discussions.

Share This Page