Friday, November 27, 2009

Norwegian Study Offers Clues

An experimental ME/CFS treatment in Norway involves some tantalizing clues: B cell depletion with Rituximab.  The study was initiated after a patient with CFS had unexpected, marked recovery of CFS symptoms following cytotoxic chemotherapy for Hodgkins's disease.  A following study was initiated recruiting patients, for B-Cell depletion therapy, all patients in the study demonstrated substantial improvement after the first infusion, followed by a relapse, improvement following the second infusion, and an even more marked  improvement after the third infusion.  This treatment will not likely gain a mainstay in ME/CFS treatment, as it poses a high degree of risk, costs over $10,000 a treatment, and would require infusions on an ongoing basis.

Nevertheless, it shows that B-Cells beyond a reasonable doubt play a major role in the pathogenesis of ME/CFS.  By depleting XMRV infected B cells, it can be seen that healthy B cells develop from progenitor stem cells, but soon succumb to infection - indicating that XMRV infects other classes of lymphocytes.  It leaves room to infer that antiretroviral therapy would have an even more profound and lasting effect: Most T-cells, with the exception of memory cells have an average lifespan of about 8 weeks. After a couple month course of antiretroviral therapy, it would not be unreasonable to see the vast majority of lymphocytes replaced by healthy cells

Fluge and Mella BMC Neurology 2009 9:28   doi:10.1186/1471-2377-9-28

15 comments:

  1. Thats a very interesting support for the XMRV finding. How about J.Kerrs finding on gene expresse
    ion in blood cells. Does it also support a possible XMRV infection? /Patrick

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  2. I'm agree with what you say and that the collapse of the lymphocytes C19 temporarily improve but important CFS symptomatology is not a causal fact.

    I know the Norwegians Dr's are doing a new study of 30 patients whose preliminary results will be available shortly and which is looking XMRV in the presence of lymphocytes
    José Luis
    Pharmacyts, de España.

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  3. Very interesting finding Patrick! I note that two opposing processes seem to be happening - some genes promoting apoptosis are upregulated, and some genes invoking cell division are upregulated, in addition to GABA A1 receptor associated protein - a protein that increases the clustering of GABA A1 receptors - interesting because GABA agonists are known to cause retrograde and anteretrograde amnesia! Interesting is also downregulation of the IL10-RA gene, which shows why the RNASE-L JAK/STAT signalling has gone awry. My conclusion: the virus has hijacked the body's defense mechanisms to ensure its survival.

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  4. Jose,

    I have seen a lot of good quality research in Norway, as compared to here in the UK. I find the establishment in the UK to be very conservative I am finding it very hard to get a research position at one of our universities, as it is not easy trying to convince the Medical Research Council to fund research for something they don't see as a priority.

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  5. I too experienced tremendous improvement in fatigue/weakness symptoms while under chemotherapy for breast cancer. For the first time in years, I could go for walks and I wasn't sure where my energy limits were. My CFS doctor told me this was not unusual.

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  6. Not surprising. Chemotherapy will in its nastiness deplete immune system cells - in this case your body was probably cleared of infected cells. It was a clue that was ignored for far too long - telling us that ME/CFS was a blood cell disorder.

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  7. I find it very important to the Norwegian study, which is the first time that CFS symptomatology disappears and reappears depending on the administration of a drug (rituximab or methotrexate) and that this improvement can be correlated with the blood concentration of lymphocytes C19 .
    What seems clear is that if by destroying lymphocytes symptomatology disappears, the problem lies within. That is a fact.
    If we think the XMRC and other viruses (EBV, CMV, HHV-6) are lymphotrophic and we have another piece of the puzzle.
    Now be wanting to know whether antiretrovirals improve the symptomatology of CFS also ...

    I know people who have improved with chemotherapy for breast cancer, precisely because it causes a depletion of lymphocytes. The funny thing is that cancer doctors (except the Norwegians) are not interested in knowing why?

    Greetings
    Jose from Spain

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  8. The reason for the huge amount of Norwegian research is the following. The geographical map of the epidemic of CFS/ME is exactly the same as the map of MultySclerosis. Therefore the highest levels in Europe are Norwey and the West Coast of Scotland. Norway, being a small very reach country can fund such research and the Government was strongly and sucessfully lobbied by the patients for the recognition of the sickness, reimboursement of the treatments and funding for reseach. It is not in vain that Dr. Kenny De Meirleir opened a clinic and research centre in Oslo last year.

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  9. Our bodies naturally make pain relievers called endorphins, but they also make other substances that can trigger pain relief in the so-called endocannabinoid system. This system seems to play a key role in many processes in the body, including modulating how we feel pain. Marijuana contains cannabinoids very similar to those that occur in the body naturally.

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  10. XMRV Positive in the UKMarch 18, 2010 at 10:06 AM

    Hello everyone. This is most interesting, especially as a patient.

    ATP/TLP (Translocator protein) function is impaired in ME/CFS, thus there is some truth in claiming that ME/CFSCFS is a 'mitochondrial disease' - although convention would say this is not the case. Why?

    In ME/CFS the mitochondria of lymphocytes are universally impaired, not muscle. In other words, it appears the ATP deficit is immune derived, suggesting the immune system is turned on. (We know it is from all the studies done on patient over the last two decades).

    RN-aseL activation (Anti Viral Pathway) would also 'use up' ATP in significant amounts, as the RN-aseL is not able to 'defend' against viruses in the normal manner, due to it's 'Low Molecular Weight' (found in ME/CFS), so it runs on full blast trying desperately to protect the person against viral onslaught - using more ATP.

    Conversely one can argue poor ATP it is not only a result of immune system 'house keeping/vigilence' and that the lymphocyte poor ATP function in ME/CFS is due to other direct factors (XMRV?) exhausting the Immune system and person infected with XMRV.

    Please note that 'Cell Free DNA' is very high in ME/CFS. What is causing the DNA to spill into the blood stream out of the cell? Oxidative stress, or XMRV? Is this how XMRV is able to be spread around the body, and cause more damage?

    As a retrovirus, XMRV infects DNA, which one could argue would cause cell break down and thus explain the very high 'Cell Free DNA' findings in ME/CFS

    Dr Judy Mikovits has stated back in October 2009, that XMRV infects T & B Cells. Thus this B Cell depletion finding makes sense.

    If I may, I have two questions. Early onset Osteoporosis is common in ME/CFS, and we know Osteoporosis can be caused by inflammation.
    We know inflammation happens in ME/CFS (elevated chemokines/cytokines), however could Osteoporosis also be caused by INFECTION of the bone marrow with XMRV, impairing bone density?

    B-Cells come from bone marrow....

    Lastly, we know that there are 'DNA adducts' found in the DNA of ME/CFS patients. DNA adducts are pre-cancerous lesions. On patients who have had this test done, some are finding they have what appears to be viral particles 'stuck' onto their DNA, as well as environmental toxins such as metals and pesticides.

    As XMRV is very new, is it possible that these viral particles 'stuck' onto DNA are actually XMRV? If so, what is the consequence for B-Cell depletion?

    Thank you for you time and interest, all the best.
    Thank you.

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  11. http://www.sangambayard-c-m.com

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  12. Good post. But I have to say that I disagree on this sentance:
    "This treatment will not likely gain a mainstay in ME/CFS treatment, as it poses a high degree of risk, costs over $10,000 a treatment, and would require infusions on an ongoing basis."

    A very similar treatment (Tysabri) is the first choice of treatment in many cases of a very similar disease (MS).

    The risk of Tysabri and Rituximab are comparable.
    Yes, it's expensive, but when the diseases are so horrible as MS and CFS are, people do pay for it. They pay for Tysabri (comparable cost) for MS patients.

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  13. http://www.sangambayard-c-m.com

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  14. Jose, when you say the Norwegian doctors are doing a study where they are looking for XMRV, do you mean the same doctors who did the Rituximab study?
    Is there any more info about a Norwegian XMRV study available?
    Also, I'd recommend the blog owner removes evision's spam.

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  15. Christine, take a look here:
    http://clinicaltrials.gov/ct2/show/NCT00848692
    It says they estimate to be done in June, but as I've understood it, from people close to th researchers, I think we'll have to wait until the end of 2010. Hopefully I'm wrong.

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