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Eradicating HMRV (or whatever they name it next)

Discussion in 'XMRV Testing, Treatment and Transmission' started by mojoey, Sep 5, 2010.

  1. leela

    leela Slow But Hopeful

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    This little piggy go BOOM BOOM BOOM all the way home.

    Interesting. Sounds promising,

    Yes, that sounds scary. We haven't got much mitochondria to spare. I'm still liking the Peptide-T idea.
  2. serg1942

    serg1942 Senior Member

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    LDN, ARVs and MLVs...

    Hi Joey and others,

    I am still trying to understand whats a retrovirus, so I'm still far away from being able to add something coherent to the great discussion you guys are having here (BTW, I am still laughing my head off with the dead piggy).

    I do apprecitte, Joey, the effort of putting together all the possible targets we may have for an antiretroviral therapy. It has been very didactic, and very useful for me, who, as many PWCs, am about to discover whether Im XMRV+ in aprox 5 weeks, and, therefore, if it turns out that I have this virus/es, then Ill have to focus my study on retrovirology (hard work!)So thanks again for the compilation!

    Ok, aside from the possible therapies that you are talking about, Id like to comment on LDN. I am one of the lucky patients to whom LDN has been a miracle. I am still very sick, but the improvement with LDN has been so dramatic that I have to say that right now its my mainstayOf course this is not cure, but I guess it is worth studying why LDN has been the only therapy that has helped me so farHere are some notes I wrote months ago about this:


    LDN has been shown to reduce the incidence of opportunistic infections in HIV-infected patients. Also, a combination therapy using anti-retrovirals along with LDN, was shown to increase the HAART efficiency and to reduce the progression of HIV infection into AIDS. In addition, methenkephalin (the main endorphin raised by LDN) was shown to have a beneficial immune modulating effect in patients with AIDS-related complex, mainly increasing the level of CD4+ T lymphocytes.

    LDN has proved to reduce oxidative stress and inflammation, to regulate the immune and endocrine systems, etc., and of course all these factors are at the core of CFS. But all this should also be accomplished by the therapies that have failed in helping me. So, which is the difference?

    LDN inhibits the iNOS enzymes, reduces inflammatory cytokines (IFN-alpha, IL-6, IL-12) and raises the inhibitory or regulatory cytokines (IFN-gamma, IL-2, IL-10). It also has antiviral and antitumoral effects (increases T CD8, T CD4, IL-2 and NK cells).

    LDN also has shown to increase the T CD4+ cells in AIDS patients, and to slow down the replication of HIV and other infections.

    LDN has also shown to increase the Th1 immune response and to reduce the Th2.

    So, back to the question: which is the difference between LDN and the therapies that should help me but that I cannot tolerate?

    It seems that by restoring the GSH levels, and therefore the redox status, we should be actually producing the same effect as with LDN, i.e., raising NK cells, improving BH4 levels and therefore reducing the formation of free radicals (by augmenting the efficiency of the enzymes iNOS), shifting the immune response from Th2 to Th1, etc.

    The two differences I can think of are:

    1.- LDN improves redox status, by reducing the production of free radicals, but not by raising the net amount of GSH, so it does not produce detoxification.

    2.- LDN improves the immune response, but at the same time, it slows down the replication of the infected cells.

    We might infer from this that either an infection and/or detoxification side effects is preventing me from tolerating the therapies Id need to take in order to heal my body.


    Ok, with this text I concluded that, maybe XMRV could be a plausible explanation as for why I cannot tolerate the supplements for the methylation cycle, or other therapies that in theory should help me, such a Hydrocortisone, adaptogens or immunostimulants like cats claw.

    Ok, the logical question now would be: Why LDN is not helping more? Obviously, the amount of endorphins raised by taking LDN is limited when you are using Naltrexone as the way to accomplish such a raise. But, what would happen if we raise these enkephalins by directly injecting them, as it has been done in cancer?

    As far as my experience, the more I raised LDN, the better I felt after passing a period of immune-reactivation (or whatever). But, unfortunately, LDN has a limit. So, if we would inject the met-enkephalins directly, we could actually overcome this limit, and who knows the result

    Does anyone know some PWC having tried these injections?

    Besides that, here are some questions for the ones who are more knowledgeable about retrovirology:

    What could be the mechanism through which LDN is actually helping to stop HIV replication? And, why ARVs seems to work better together with LDN?

    Could LDN be this immune-modulator that wed need in the ideal cocktail against these MLVs???

    Well, just some thoughts that I wanted to share with you

    Saluditos,
    Sergio
  3. xrayspex

    xrayspex Senior Member

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    I did LDN for 6 mo.s with some benefits, but it did seem to make my brain react even more chaotically to even more substances, like foods and supplements etc it got too hard to figure out and also when pain flared up at end from irritating neck the LDN couldnt handle the pain well enough so went back to using propoxyphene, low dose, regularly, had been doing that prior for most of new millenium and on and off in the 90s.
    I am wondering if propoxyphene and perhaps opiates/opioids, certain ones certain doses, behave like LDN w/immune system, I have stayed at about 60 kps most of the 21 years since onset with flares doing worse and some periods minutely better, but without the pain control would not have survived it also seems like the pain med helps reduce or delay the oxygen hunger. Seems like this should be explored more but I think there is a stigma around that sort of medication, one of the reasons don't bring it up a lot. I have been fortunate not to build much of a tolerance, am a lightweight, always have been with meds and before with alcohol, can't drink at all, very sensitive.
  4. mojoey

    mojoey Senior Member

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    More on error catastrophe (the extinction of a retrovirus as a result of excessive RNA mutations):

    When I was reading about KP-1461, I found that the apobec3 enzyme systems are the innate enzymes in our cells that hypermutate the virus. When I did some more digging, I found that the initial study that talked about the efficacy of AZT, Tenofovir, and Ralt had already discussed the antiviral effects of apobec3g (A3G) and apobec3f (A3F). Re-read yourself: http://jvi.asm.org/cgi/content/abstract/84/11/5719

    However, another study http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909211/ found that A3G is the only effective human apobec3 protein versus XMRV but that murine apobec3 (ma3) may be partially effective against XMRV:

    Wikipedia on A3G:

    I've emailed the author of these studies to ask about therapeutic applications of these proteins.

    So in summary, we now have 6 drugs or proteins that can induce lethal mutagenesis at least in vitro.

    1) integrase-derived peptides
    2) human A3G
    3) murine A3
    4) KP-1461 (experimental AIDS drug)
    5) gemcitabine (chemo drug) and
    6) decitabine (chemo drug)
  5. leela

    leela Slow But Hopeful

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    Brilliant detective work as usual, Mojoey.

    Here's the bit I don't get
    I presume I'm reading it wrong but it looks like they are saying they looked into how XMRV uses A3G proteins to evade the suppression of replication?
    Then they go on to say that expression of same inhibits replication? :confused:

    Please clarify?
  6. Daffodil

    Daffodil Senior Member

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    hmmmm...so that may be why they keep talking about cancer drugs for CFS....good work joey!
  7. mojoey

    mojoey Senior Member

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    They're not looking into how XMRV uses A3G to do anything; XMRV has no positive use for A3G. They were studying in which cells APOBEC3 proteins are not as effective in inhibiting replication of XMRV to identify in which cells XMRV was more likely to evade suppression. The wording was just a bit confusing.

  8. xrayspex

    xrayspex Senior Member

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    I didnt take bio and chemistry in college and wasn't awesome at it in high school, I love that some of you guys can follow this and research into it but could you once in the while put it in laymens terms? the suspense is killing me. So the bottom line I am getting from some of the threads on xmrv/hgrv treatment is that haart and chemotherapy may be the road to take.
    What was that thread about depakote found to may be useful with aids, that could probly be easy enough to get access to anytime.
    I am trying to decide my next move, I have nasty MCS and have to pulse even valtrex or artesunate or wormwood practically homeopathically when I try them infrequently, not movitated to feel like crap more than I do for extended periods unless I feel like there is a for sure pay-off. Reluctant to do clinical trials since can't control the dose myself but on other hand am 50 yrs old now with this cfs 21 years so time to do something. Hoping can consult at WPI perhaps and do something at home. Work parttime so not sure if want to take a big medical leave to do something but may have to as whatever I try if anything will likely hose me if I take it regularly.
  9. leela

    leela Slow But Hopeful

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    Chemo sounds like a terrible idea for people who are already immuno-suppressed, overloaded with toxic materials, as well as chemically sensitive.
    I personally would see chemo as a really slow painful suicide option....
    Call me crazy.
  10. leela

    leela Slow But Hopeful

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    Thanks. I knew I was reading it wrong. :ashamed:
  11. mojoey

    mojoey Senior Member

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    Leela-

    That's what I thought until CFS patients reported remission from Rituximab, b-cell depletion and cancer patients with CFS reported remission from cancer-related chemo. I have MCS and have issues with toxic drugs like most CFS patients, but if a drug is targeted enough, we won't need very high doses of it (the 2 chemo drugs listed above were used in low doses compared to when used for cancer radiation).

    Call me crazy but lifetime HAART sounds like the most toxic option of all!
  12. mojoey

    mojoey Senior Member

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    Hey Sergio,

    Very interesting that LDN worked whereas the others didn't. I agree that immunodulation is the likely explanation... why else is it that ampligen has such a track record when, compared with all the other stuff we're taking, it seems much more toxic in theory? Especially since it increases NF-Kappa B, which supposedly should be downregulated at all costs to prevent XMRV reactivation.

    I also agree that immune modulation will need to be part and parcel of any anti-XMRV strategy. Peterson said that anyone that truly understands retroviruses thinks as much. One theory for why rituximab helped is because by depleting the b-cells the drug killed off much of the excess inflammatory response. I'm thinking both that and wiping out a good chunk of XMRV are likely explanations.

    Can''t answer your question about injecting the enkephalins directly, but one thing to keep in mind is that too much of anything is rarely good for CFS patients. Ampligen induces interferon (via the NF kappa b activation), so you would think we could just get straight interferon but Peterson said that makes patients very sick.
  13. leela

    leela Slow But Hopeful

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    I'm with you on that, crazy or loco!
  14. leela

    leela Slow But Hopeful

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    Sergio,

    For someone whao was concerned about having something coherent to say, you certainly gave an excellent picture of LDN etc.
    Thank you for that clear, thorough, and articulate account. It is very useful.
  15. xrayspex

    xrayspex Senior Member

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    serg said: "What could be the mechanism through which LDN is actually helping to stop HIV replication? And, why ARVs seems to work better together with LDN?
    Could LDN be this immune-modulator that we’d need in the “ideal cocktail” against these MLVs??"

    A friend of mine doing ampligen with Peterson had to go off of meds and any pain meds before and during it. I am wondering if LDN would also be disallowed with ampligen? I don't quite understand why can't take pain meds with ampligen, does that mean people shouldnt use them with valtrex, acyclivor or even HAART either? I think LDN and opiates work very similarly, but obviously in dif way. LDN freaked me out in a way because at times it seemed anything that increased my endorphins caused a neg reaction from the ldn and I started to get depressed at the end, but it did help minimize average pain very well. I just don't feel comfortable ever taking again anything that messes with blocking my endorphins, can backfire.
  16. Daffodil

    Daffodil Senior Member

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  17. serg1942

    serg1942 Senior Member

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    Joey, xrayspex, Leela: thoughts on avaiable treatments for RVs...

    Hi Joey,

    Yeah, of course immunemodulation seems to be one of the clues, and in this regard Gc-MAF was one of my main hopes, but I am also concerned about the macrophages being reservoirs of MLVs…Anyway, it seems that there’s still nothing clear with this therapy yet…

    On the other hand, it’s really helpful the compilation work you and others are doing here…Certainly it’ll help me (and others!) to have something specific to start studying the subject. Surely I’ll have a huge incentive to dive in to this new world when I receive my XMRV results from VIPdx, providing they are positive (Yes, I do want to be the first Spanish guy (that I know) in having this virus, being stigmatized, repudiated, etc…jaja!)

    Having said the above I have to recognize that I feel some scared, as I don’t like at all the idea of following the treatments that seem to be more promising (all the promising this can be, being everything so experimental, and focused mainly on HIV), i.e., HAART or chemo drugs…Call me nave, but I’m still hopeful in finding a nosode, or something similar to treat this retroviruses in a much safer way…

    I don’t know, everything seems to be weird, in the sense that when I was studying the biochemistry behind the CFS during the last years, I was convinced that it was the way to go…Everything made sense, and everything seemed very clear…But for some reason there’s something we’re missing…And now, on the other hand, although a retrovirus could be a plausible explanation, the possible treatments are so dangerous, that actually I don’t want even to consider them, although I need to study this options, as there’re no other possibilities right now…

    Hi Leela,

    Thank you, but I meant I have no idea about retrovirology, so all this stuff sounds to me as Chinese! (hey, no offence to chineses, it’s just an Spanish expression! ;-) In other words, I have to study how a retrovirus behaves, etc., before I am able to actually think about this and make my own conclusions about the next steps to take treatment-wise…I guess all we PWCs, if finally turn out to be “hosting” a retrovirus/es, will have to change our mind in many aspects…

    Hi xrayspex,

    I don’t really think that LDN can backfire, as there’re many reports on people with Multiple Sclerosis, who have been taking LDN for 10-15 years, and the effect is sustained without a sign of opposite effects…It can loose effectiveness over time if Naltrexone accumulates in the body, but this situation is easily solved by taking it every other day, or by reducing the dose. By taking LDN you are just blocking your opioid receptors about 4 hours daily (Ideally while you’re sleeping to avoid depression), but the rest 20 hours your body is actually “high” on endorphins… :)

    Saluditos,
    S.
  18. xrayspex

    xrayspex Senior Member

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    Serg, I know what you are saying about LDN, I do, I researched it heavily in 2008 before i took it and I initiated getting a script from a doc, totally my idea, and I went thru hell going off propoxyphene from the LDN as the LDN gave me very weird w/d that I never normally get going off propoxyphene, brainsplitting killer headaches even after 3 days off from the normal daily routine of 2 60mg propoxyphene (3 days is all Skip in Fla had rec'd) which one chick on LDN can even take darvon w/her LDN (she hosted a website on LDN) but not me! I am thee princess and the pea of MCS.

    Anyway, I went thru the hell, had to play with the dose immensely, finally got stablized after a month or so on like a homeopathic amount, forget, like .5 of a mg, and it helped with my chronic pain and fatigue (as well as propoxyphene had) for 6 months, I am not sure what else it did, but I did have normal interleukins 6 mo.s later (although I dont know what they were before LDN, my rnase and natkiller cells were abnormal post LDN though). I did become very sensitve to more foods though during the time I was on LDN is what I was trying to say, I interpreted it as my body got confused on when to block endorphin inducing stuff, it didnt work like clockwork, the LDN with me, I think I even skipped some days as with me a little goes a long way. And trust me, I have chronic pain I wouldnt have skipped days if it wasnt working. But what happend is hit my head on the car door after 6 months and flared up my fragile neck and ldn could not handle the heavy duty pain, and I realized I do not, with a fragile cervical spine, EVER want to be in the position again where I cannot take a pain med if I need it. I do not recommend against LDN, if someone can't handle pain meds or if they dont have a bad spine I think its wonderful to try, also if you arent hardcore mcs and your brain doesnt get confused too easily with meds, a better tolerance than I. I think there is good research on LDN. I do feel bad for addicts who are forced on naltrexone and might get the mind numbing depression cus its blocking their endorphins and not just drugs. Some people get that reaction I read it on erowid and I think that is sort of what happened to me, its not fun, to have joy blocked from happy moods that are natural or chocolate, there is that one doc that gives LDN to autistic kids and I read at that site that they had some of same troubles as me, it got confusing to know what is your real food sensitivity or what is the LDN making your body sensitive to the endorphin producing action of the food etc. This is just my experience and opinion, again, I am not against it but I am just saying it is not a onesize fits all panacea, but fab to try.

    -------
    serg, others, on a dif note, what do you think of the peptide t of candace pert? I like the idea of less harsh medicines for cfs, I wonder about pulsing a couple different things, I am sort of trying that haphazardly ths summer with valtrex and at times a little wormwood or artesunate, I think for me not taking an annihilating approach is kinder perhaps better in long run, esp since my kps is 60ish.
  19. mojoey

    mojoey Senior Member

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  20. mojoey

    mojoey Senior Member

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    Hey Serg,

    I don't wanna sound presumptuous, but I really think we're on the same page here. Although my understanding and ability to digest large quantities of biochemistry has been way below yours, there have been a few points when things really made sense to me and I felt like I had control over the situation. However, each of these times I've been wrong. Like you, I tried more than a year of Methylation, even went full Yasko, and got worse in the process. I thought I was on the right path treating lyme, bacterial co-infections, viral co-infections, because I actually felt a bit better doing so, but once I ran out of infections to treat I started dropping again. Like you said, retrovirus(es) are a plausible explanation for why some things worked and why others didn't, and why nothing has gotten us to the finish line. I understand the fear of researching something because of the consequences (HAART) are not so salivating, but the consequences are dynamic. As we research more, we're finding there are more routes to go than HAART, and certainly some of them are far less toxic (i.e. peptide and gene therapy).

    I also echo your concern about gcmaf. That's why I've never been able to fully understand why it would eradicate a retrovirus.

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