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Ron Davis latest: more evidence of "something in the blood" (Simon M blog)

Discussion in 'BioMedical ME/CFS News' started by Simon M, Dec 10, 2019.

  1. Kitty

    Kitty Senior Member (Voting Rights)

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    I don't think this has been published, even in the PNAS article – you might have to find a contact for Rahim Esfandyarpour to find out. Only the two mentioned above restored the signal to something like normal, so those are the ones that tend to have been discussed.
     
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  2. Sean

    Sean Senior Member (Voting Rights)

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    It is a good question about whether it is (more or less permanent) damage, or a long term and reversible adaption to a different plasma environment.

    It would be interesting to see what happens to ME cells left in healthy plasma for an extended period, and vice versa, with healthy cells left in ME plasma.

    Don't know how feasible an experiment it would be, but it would be interesting.
     
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  3. tuha

    tuha Established Member

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    Thanks Simon for your blog :)
    Maybe it´s stupid question and maybe it´s even not possible to answer it but how difficult it can be to find that "something in the blood"?

    I find this interesting:
    Davis has previously talked about his team’s work to home in on the presumed “factor” in the blood. They start by splitting the blood, physically or biochemically separating its components into separate fractions. Then, they test to see which fraction of the blood contains the mystery factor. The next step is to split the “active” fraction into still further fractions, and so on.

    How many things do they have to eliminate step by step to find that "something in the blood" what is maybe causing our problems?
     
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  4. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    There is a bit more info on the current situation in @Ben H talk that @Sly Saint posted and included a YouTube transcript
    https://www.s4me.info/threads/me-cf...-bedside-chat-with-ben-h-and-ron-davis.12771/

    Rahim the researcher who "owns" the design of the nanoneedle moved from Stanford to UC Irvine earlier in the year. Only recently did he get a student at his new institution to work on producing another batch of chips and at the time of the video they had not yet tested them to see if they worked. If not, another batch would have to be made.

    YouTube Transcript
    Ron commented that you really need to be able to test many samples at the same time. He wants to get the technology reliable, "mass" produced, and the experimental procedure optimised (%of salt, amount of solution etc) so that test units can be "exported" to other researcher labs. As yet they are not able to get good repeatable results with frozen blood so the need for fresh blood is another limiting factor. This will take a redesign and development effort.

    An NIH grant was submitted earlier in the year to fund this work faster and they are waiting to hear if it is approved any time now.
     
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  5. JES

    JES Senior Member (Voting Rights)

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    Regarding the thing in the blood, while I think it would be important to figure out exactly what it is, finding it wouldn't necessarily solve the puzzle. There was another thread about failed Alzheimer's research. The prevailing hypothesis used to be that amyloid beta was the factor that caused or at least served as a main driver to the disease, but from the latest understanding, it seems like amyloid plaques are probably better described as a consequence of the disease.

    Using the Alzheimer's research analogy, it could be that the "something in the blood" finding isn't close to the actual root cause of ME/CFS. If that is the case, the next problematic is what is causing the factor in the blood to form, and so on. From thereon you may end up back to cytokines and the immune system and eventually you have completed the circle. So yeah, I'm not envying the task ahead of ME/CFS researchers.
     
  6. Ben H

    Ben H Established Member (Voting Rights)

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    It would be interesting though I imagine cell lysis would be an issue.

    But, and this is a BIG but, if this is correct, if this is what is happening in-vivo, if the mentioned compounds work in-vivo, and if the offending molecule(s) causing the impedance signal are removed or attenuated (these are all huge 'ifs')...when new cells are made over time, there would hopefully be no lasting damage. Because they wouldn't be exposed to the offending molecules(s) from the start.

    Massive conjecture here.


    B
     
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  7. Badpack

    Badpack Established Member (Voting Rights)

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    I still hope that the something in the blood keeps being true, but i got a cycle of 7 plasma exchanges 2 months ago. Did absolutely nothing for me. Doesnt confirm or deny anything. Still i would have hoped for a change for the better if you believe its something in the plasma.
     
  8. Forbin

    Forbin Senior Member (Voting Rights)

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    Even if the only use of the nanoneedle technology was its ability to reliably distinguish ME/CFS patients from controls, it would still be a huge step forward for research.
     
  9. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    @Badpack

    Is it possible that the plasmapheresis did not remove the “bad stuff” (exosomes) because they were not the right size? I assume that plasma filters are designed to remove specific size antibodies and maybe the “something in the plasma” was too small to be removed by the filters?
     
  10. alex3619

    alex3619 Senior Member (Voting Rights)

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    I would really like people with mitochondrial disorders to be tested. No salt response, full response, or mixed response would all tell us something. If the mixed response relates to specific mitochondrial disorders and not others it would tell us a lot.
     
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  11. alex3619

    alex3619 Senior Member (Voting Rights)

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    Correct, but misleading. With a target that may be a mediating step for our energy loss we can develop new drugs, repurpose old ones like the SS drugs, and so on. Its something that is potentially treatable. While knowing the root cause may be very important for a cure, knowing mediating mechanisms is very important for treatments.
     
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  12. alex3619

    alex3619 Senior Member (Voting Rights)

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    I suspect the nanoneedle test will NOT distinguish ME/CFS from mitochondrial disorders. However it may be that the existing diagnostic protocols, such as CCC or ICC, PLUS the nanoneedle test, might be enough.
     
  13. Simon M

    Simon M Senior Member (Voting Rights)

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    Janet Dafoe has posted a very helpful note from Ron Davis on PR explaining in much more detail the status of the nanoneedle project and work to find something in the blood:

    [Janet]
    There are a lot of various threads and tweets about this so I asked Ron to clarify where the research is at and what the plans are. As for everything else, this has gone a lot slower than it could have if he'd had more funding. The fact that he's gotten this far i totally due to patients' contributions to Open Medicine Foundation and to Stanford's ME/CFS Collaborative Research Center.

    From Ron:

    As you know, we have found that there is something in patients' plasma that is largely responsible for the signal that we see in the nanoneedle assay. We have some preliminary results using filtration that indicate that the major plasma component is fairly large, suggesting that it is not a cytokine.

    We would like to identify what the component, or components, are that causes this signal, which could give us good insight into what's happening with the patients.

    To conduct these experiments, we will need to fractionate the plasma using a variety of techniques, such as size fractionation. To fractionate means to divide the plasma up into multiple components based on various parameters. For example, to fractionate by size means to separate the plasma into 10 to 100 different parts, increasing in size.

    We then need to run all these fractions in the nanoneedle at the same time, using the same blood sample. This is important, because if we run them one or two at a time there could be differences that are due to the different runs, rather than differences in the sample itself.

    Currently, we are relying on a commercial instrument, costing $30,000, that is only capable of running 2 nanoneedle chip samples per day. Also, the sample needs to be run within 24 hours of the blood collection. Therefore, using the current machine, we would have to get new blood samples every day. We can't have the same patient come back every day and we can't use lots of different patients for different fractions, because people differ and this is just too much variance to yield anything useful.

    What is now necessary is to fabricate a new electronic control system that can collect the data from the nanoneedle allowing it to collect data from up to 100 chips simultaneously. That way, all the fractions from the blood sample of one patient can be run simultaneously. Rahim Estfanyarpour, who developed the nanoneedle, has been working on this.

    However, since Rahim has taken a professorship at UC Irvine, he has had to set up his whole new operation, get new students, and train everyone. He has been coming up to Stanford and collaborating with me every week. He has submitted a grant to NIH for this project. Meanwhile, he has been funded by OMF to pursue this new machine and to make new chips. He has now delivered a large new batch of chips.

    We are now able to use the new chips to test various drugs, and we will use them in the new machine for fractionated plasma as soon as:

    1. We have the new machine working
    2. We have developed the fractionation method(s)
    3. We have the new chips working with the new machine
    4. We have solved all the problems that come up in the process

    The current machine that runs 2 samples and collects the data from the nanoneedle costs $30,000 to buy. We don't need all the versatility of this commercial instrument. The machine that Rahim is developing will run up to 100 samples and will cost a few hundred dollars.

    We are working as fast as we can to get this into operation.

    I hope this clarifies some of your questions.

    Ron Davis
    [Originally posted on 11.12.19 (UK, probably the 10th in California)]
     
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  14. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    If I remember right from @Andy's Q&A video with Karl Morten he said he would add an experiment to his wish list to look at cellular respiration using the same salt solution + plasma + cells to see if oxygen consumption differences can be seen.
     
    Last edited: Dec 11, 2019
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  15. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    I'd also like to point out that Alain Moreau presented at the Stanford Symposium in September and at the NIH conference in April about his use of the CellKey cellular impedance analyser and how he was testing compounds and measuring impedance changes in Jurkat cells soaked in patient plasma. So while not using a salt stress test he is trying to see how different groups of patients plasma have differing effects on a purchased reference Jurkat cell impedance when treated with compounds.
    MoreauJurkat.JPG MoreauJurkat3.JPG
     
    Last edited: Dec 11, 2019
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  16. Sisyphus

    Sisyphus Senior Member (Voting Rights)

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    Something in the blood could be a result not a cause. Medicine knows how to ‘look’ into blood and can easily get a sample. Variation of finding things under a lamppost.*

    *This is not meant to denigrate the research in any way, just to point out that research usually looks in places where they can get a flashlight into easily or at all with a live subject. Nature is not required to place the source of our problem in a place we can examine, nor to make what’s broken a defect we can detect.
     
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  17. Mij

    Mij Senior Member (Voting Rights)

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    Isn't that what ME is? The original triggering event is no longer present. Aren't most chronic illnesses caused by the biological reaction to an injury, and not the initial injury?
     
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  18. borko2100

    borko2100 Established Member (Voting Rights)

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    If there is indeed something, then the next step is finding the source. What could be generating such a harmful substance? A virus? The immune system? Something else? Fascinating.
     
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  19. Kitty

    Kitty Senior Member (Voting Rights)

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    It's not even necessarily harmful. We could be producing an abnormal reaction to something that's perfectly normal and will be found in everyone's blood at times. That's what makes it so complicated – we may need to identify both the substance and whatever it's setting off. :confused:
     
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  20. Forbin

    Forbin Senior Member (Voting Rights)

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    It also could be the amount of something in the blood. There could be too little (or none) of something in the blood that's necessary, or too much of something that may or may not be necessary but which is toxic at high levels.

    High on my list of suspects would be some metabolite created by a species of microbe in the gut - specifically deep in the small intestine where molecules are absorbed and it's hard to sample and study what's going on [just my personal speculation].
     
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