Professor & patients' paper on the solvable biological challenge of ME/CFS: reader-friendly version
Simon McGrath provides a patient-friendly version of a peer-reviewed paper which highlights some of the most promising biomedical research on ME/CFS ...
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Enterovirus and treatments

Discussion in 'General ME/CFS Discussion' started by knackers323, Oct 15, 2014.

  1. knackers323

    knackers323 Senior Member

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    I've been doing a bit of reading and I've found a few things other than oxymatrine that may possibly treat enterovirus, that Dr Chia does no seem to use.

    Ribavirin

    Pleconaril-as yet I available to the public, but there are apparently ways to get it.

    Nitazoxinide

    Interferon suppositories- if a dr cannot be found to supply intraveinusly

    DRACO-again not available to the public. Could probably be obtained but probably cost prohibative.

    Has anyone tried any of these things?

    Or know ofanything else that has been effective?

    Or know why Dr Chia does not use them?
     
    Last edited: Oct 15, 2014
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  2. ukxmrv

    ukxmrv Senior Member

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    Amantadine was used by the NHS in the UK on some of the 1980's ME patients who tested positive for VP1

    Not sure why he doesn't or does use particular things. At his IiME talk in London I remember that he did try various things on his son but can't remember what they were sorry.

    p.s. interferon/ Chia/ Rib rang a bell with me and I searched and found this

    "it was his success in the treatment arena that convinced Dr. Chia he had found a major cause of this disease. As with his diagnostic work, Dr. Chia’s learning curve in the treatment arena was steep. His son Andrew’s case provides a case in point. Andrew had a Coxsackie (enterovirus) infection. Early attempts to use ribavarin resulted in reduced titers and improved health, but were followed by a quick relapse. Ribavarin plus interferon seemed to result in a complete return to health, but after Andrew pushed too hard on a vacation he relapsed badly and his antibody titers shot up (320) and stayed that way for 3-4 years."

    http://phoenixrising.me/interviews-3/the-dr-john-chia-interview-with-cort-johnson-808-introduction
     
    Last edited: Oct 15, 2014
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  3. halcyon

    halcyon Senior Member

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    Take a look at his 2005 paper. He has used Ribavirin, Pleconaril, and interferon. It seems the main reason he abandons treatments is due to lack of long term efficacy. High cost and nasty side effects are also considerations.

    I'm not familiar with Nitazoxinide.

    As @ukxmrv mentioned he is currently using Amantadine as an adjunct treatment. I've also heard from another patient that he's using Epivir. @Patrick* just reported on his blog that he suggested use of Prozac (for it's antiviral effects) in combination with interferon.

    It seems the general idea is that you combine endogenously produced interferon (stimulated by oxymatrine) with some form of antiviral to try and halt viral replication and keep the chronically infected cells at bay. So far, as far as I have read, there isn't anything that can deal with the double-stranded RNA that seems to be the crux of the matter. The interferon stimulates RNase L which can degrade single-stranded RNA but is ineffective against the double-stranded RNA in these chronic enterovirus infections.

    Our cells do produce an RNase III enzyme called DICER which is supposed to be able to degrade double-stranded RNA, but it's unclear why this doesn't seem to clear the chronic infection.
     
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  4. halcyon

    halcyon Senior Member

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    Inosine is another adjunct treatment that he seems to use as well.
     
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  5. halcyon

    halcyon Senior Member

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    I just came across this paper from earlier this year. It goes over a whole bunch of methods of interfering with enterovirus, mostly in the context of EV71, but I'm sure a lot of it could apply to other enteroviruses. Sadly it seems like it's mostly research compounds that haven't gone beyond in vitro or in vivo murine testing. You can skip to Figure 1 and Table 1 to get the meat of it if you don't want to read the entire paper.
     
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  6. knackers323

    knackers323 Senior Member

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    Thanks for the answers guys.

    @halcyon I'm surprised the pleconaril doesn't work.

    Anyone know if Chia ever finds entero in the blood and what this indicates? Larger infection, beginning of infection etc.
     
  7. halcyon

    halcyon Senior Member

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    In Chia's study the Pleconaril did work for 1 out of 4 patients, but she relapsed shortly after treatment. Pleconaril was denied FDA approval and isn't available anymore anyways.

    Yes, he did find virus in the plasma and PBMCs as reported in his paper. Check out this table. The interesting part is that he found patients blood samples would fluctuate between positive and negative for enteroviral RNA over time.
     
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  8. halcyon

    halcyon Senior Member

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    You can read about his study on the use of Ribavirin and Interferon-α here. It's more of the same though. Slight symptomatic improvement and lowering of antibody titers during treatment, but eventual relapse of symptoms and elevation of antibody titers after treatment ended.
     
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  9. Hip

    Hip Senior Member

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    Although nitazoxanide is a broad-spectrum antiviral that works for a number of viruses, I could not find any indication that it definitely works for enteroviruses.

    This study said:
     
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  10. knackers323

    knackers323 Senior Member

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    How long has this Ebola outbreak been around, and they are already talking about treatments and vaccines.?

    So it can be done if they want to. Or do I have this wrong?

    The interferon therapy that he uses sounds as though it gives remission for a year or so. Is there any reason why this cannot be done yearly to keep a person well? Apart from the cost.
     
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  11. Hip

    Hip Senior Member

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    A coxsackievirus B vaccine is very feasible, and I started a thread on this. If this vaccine were introduce, there's a good change that is would eliminate most cases of ME/CFS in future generations (not much good for us though).

    DRACO would likely destroy nearly all viruses, and quite possibly cure ME/CFS, but nobody want to fund the research. There is thread about DRACO crowdfunding here.


    I was also wondering the same thing about getting regular interferon therapy once each year, to keep ME/CFS at bay.

    I know the IFN treatment is hard to bear for many. There can be high depression as a side effect for many months. And the cost is high, around $15,000 for the three month course of interferon treatment. It could be that interferon takes a high toll on the body, so that you cannot take IFN all that often.

    Or perhaps patients don't always respond well to additional courses of interferon. In this article on Dr Chia's interferon treatment, it says "some patients responded well to another course of interferon".

    And Chia saw that in many ME/CFS patients, after a course of interferon, the relapse back into ME/CFS happens so quickly that its not worth it. If you read the same Chia interferon article, you see that most patients returned to full time work after a course of interferon, but then relapsed after just a few months; very few patients lasted a year before they relapsed (the ones that lasted a year before relapse were on the IFN alpha + IFN gamma combo).
     
    Last edited: Oct 26, 2014
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  12. Hip

    Hip Senior Member

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    The antiviral effects of interferon on enteroviral RNA infections in our cells work through the release of RNase L.

    Interferon triggers the release of RNase L in cells, which in turn destroys viral RNA in the cell. But in ME/CFS it is known that the RNase L gets chopped up (cleaved), making it less effective at destroying the viral RNA in the cell.

    Now, it is calpain that actually does the chopping up of RNase L.

    So I was thinking that taking calpain activation inhibitors might help prevent RNase L being chopped up, which would then allow it to do its work of clearing out enteroviral RNA from out cells. There are in fact a number of calpain inhibitors:

    Calpain activation inhibitors:

    • Taurine 50 mg per kg (= 4 grams dose for a man) markedly reduced m-calpain activity.
    • Glutathione
    inhibits calpain activity.
    • Luteolin reduced calcium influx and inhibited calpain activation.

    Then there also are some drugs that inhibit calpain, such as calpeptin and calpastatin.



    Calpain is activated when there is a calcium influx into cells such as neurons and astrocytes, which occurs when the NMDA receptors on these cells are activated. It thus occurred to me that in ME/CFS there may be a vicious circle going on in the brain, with NMDA activation, calcium influx, calpain activation and RNase L cleaving, which is as follows:

    Vicious circle in the brains of ME/CFS patients involving NMDA activation, calcium influx, calpain activation and RNase L cleaving

    (1) Due to brain infection and the resultant brain inflammation, ME/CFS patients may have high extracellular glutamate in the brain, since brain inflammation is hypothesized to elevate glutamate.

    (2) Extracellular glutamate in the brain over-activates the NMDA receptors on brain cells, thus causing excessive calcium influx to the cell, and high intracellular calcium.

    (3) High intracellular calcium activates calpain, which then cleaves the RNase L and prevents viral clearance.

    (4) This then maintains the viral infection in the brain, leading to further brain inflammation, which completes the vicious circle.

    If this vicious circle model is correct, then another way to inhibit calpain activation would be to reduce extracellular glutamate in the brain, and/or block NMDA receptor activation.



    Dr Kenny De Meirleir published a book focusing on RNase L in ME/CFS, and this book examines how high levels of calpain in ME/CFS act to chop up RNase L.

    Of the two main types of calpain, μ-calpain and m-calpain (also called calpain 1 and calpain 2), De Meirleir says it is m-calpain that is linked to the cleavage of proteins the PBMCs of ME/CFS patients (ref: here).
     
    Last edited: Nov 5, 2014
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  13. halcyon

    halcyon Senior Member

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    Hip,

    Interesting thoughts on calpain. It seems, though, that RNase L is not effective at degrading dsRNA. Chia mentions this in his 2005 paper:

    "Among other immunostimulatory effects, double stranded RNA is a potent inducer of interferon synthesis, which activates intracellular RNase, with resultant degradation of excessive single stranded RNA. The finding of a higher level of RNase L activity in the mononuclear cells of patients with CFS is consistent with this paradigm.53 54 However, enough positive and negative strands probably recombine to form stable double stranded RNAs, which are resistant to RNAse L inactivation, and the life cycle will start again when the pressure of the immune response decreases."

    I've seen this stated about RNase L elsewhere as well though I'm having trouble finding where I saw it. As I mentioned above, the RNase III enzyme Dicer is supposed to be able to degrade dsRNA but apparently this isn't working well enough in these chronic enteroviral infections. It seems like figuring out how to deal with the dsRNA is the key to this whole thing.
     
  14. Hip

    Hip Senior Member

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    That's very interesting, @halcyon, I didn't see your above post on the RNase III enzyme dicer, which destroys dsRNA.

    So dicer might have a very good antiviral effect for enterovirus-associated ME/CFS patients, who are supposed to have intracellular infections of enteroviral dsRNA in their cells (ie, non-cytolytic enterovirus infections).

    In terms of what induces and inhibits dicer, this study found:

    Dicer inducers:
    • Interferon gamma

    Dicer inhibitors:
    • dsRNA
    • Type I interferons (such as interferon alpha, beta and delta)
    • Reactive oxygen species
    • Phorbol esters

    First of all, it makes no sense to me why dsRNA would inhibit dicer, if dicer's function is to destroy viral dsRNA in cells. But let's leave that aside for the moment.

    It looks like interferon gamma is the interferon you need to boost dicer levels. In fact there are some herbs that stimulate interferon gamma. It's interesting that out of the different types of interferon Dr Chia tried on his ME/CFS patients, it was the interferon alpha + gamma combo that was able to place two ME/CFS patients into full remission that lasted for 14 months before relapse (see the Chia interferon article I cited above). I believe this was the best result that Dr Chia obtained with interferon.

    So perhaps with interferon alpha + interferon gamma together, you will ramp up both RNase L and dicer, which has a more potent antiviral effect.

    The study also found phorbol esters inhibit dicer, and interestingly, these have actually been associated with triggering ME/CFS, in that tung oil, a wood preservative which contains the phorbol ester HHPA, has been linked to ME/CFS.1 2



    It states in this study that:
    So when calpain cuts up dicer, it seems that it increases dicer's acitvity. However, this study is in the context of neuronal synapses and dendrites, rather than antiviral activity of dicer, so this result may not apply in the antiviral context. The study does certainly show that calpain can cut up (cleave) dicer, though, so this may have well have consequences for ME/CFS.



    In terms of this process where positive and negative strands of enteroviral RNA made inside an infected cell likely combine to form dsRNA, which is resistant to RNAse L inactivation, I guess that RNAse L is still useful for destroying these positive and negative strands of RNA, hopefully targeting them before they can combine to form the more resistant dsRNA.
     
    Last edited: Oct 16, 2014
  15. knackers323

    knackers323 Senior Member

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    Awesome work @Hip how potent are the herbs that raise interferon gamma?

    I may have asked this before but you know if the interferon suppositories are effective?
     
  16. Hip

    Hip Senior Member

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    Don't know about interferon suppositories, but in general interferon is very expensive.

    Here is a list of interferon gamma boosters. Some may be more potent than others.

    Interferon Gamma Boosters:
    Neem (Azadirachta indica) 1
    Reishi (Ganoderma lucidum) 1 2
    Cordyceps 1 2
    Echinacea purpurea 1 2 3 (conflicting studies)
    Astragalus 1
    Astragaloside (from Astragalus) 1 2
    Ginseng Korean 1
    Propolis 1
    COLD-FX American ginseng extract 1 (significantly increases IFN-γ )
    Germanium sesquioxide 1
    Goji berries (wolfberry) 1
    Glycyrrhizin (from licorice) 1 (I think this is quite potent)
    Silymarin (from milk thistle) 1
    Selenium 1
    Human growth hormone (HGH) 1

    Immunomodulators that shift from the Th2 to the Th1 immune response should also increase interferon gamma, because interferon gamma is one of the Th1 cytokines (along with IL-12 and IL-2).
     
    Last edited: Oct 26, 2014
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  17. PDXhausted

    PDXhausted Senior Member

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    I thought enteroviruses were single-stranded?
     
  18. halcyon

    halcyon Senior Member

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    They normally are. In chronic infections, viral replication becomes defective and loses the ability to lyse the cell and complete the lifecycle. In addition, negative strands are produced in far greater numbers, making a 1:1 ratio of positive to negative strands (normally there is a 100:1 positive to negative strand ratio as the negative strand is simply used as a template to replicate more positive strand copies). These two factors seem to lead to the formation of stable double-stranded RNA in chronically infected cells.
     
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  19. PDXhausted

    PDXhausted Senior Member

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    @halcyon Very interesting! Thank you for explaining that.
     
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    @Hip is correct. Nitazoxanide had NO effect when I trialled it. It is not mentioned on the Enterovirusfoundations website either.

    I find immunovir alone helpful - recomended by the EV foundation.

    Quercetine another - recomended by the EV foundation.

    My friend who also has EV has found the combination of IMI Cycloferon and IVI GSH **massively** increased his NK cell numbers & immune function.

    Cycloferon alone does NOT seem to have the same effect.

    Chia uses oxymatrine then adds Inosine if that does not work he swops to oxymatrine and amantadine if that does not work oxymatrine and epivir.

    In my correspondence with EV Med with the VP1 testing I had primarilarly via Lucila Chia, I was informed Pleconaril does not work once the virus "penitrates the cell" - maybe the academics here can define what that means exacterly?

    INF is upwards of $5000/month.

    Chia reserves INF for the "spring loaded immune response" of a patient stopping oxymatrine prematurely as INF use allows the recommencement of oxymatrine, in most cases.

    I think like Hip outlined a natural combination of compounds is a feasible treatment option.
     

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