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Rituximab, a Possible XMRV Treatment?

Discussion in 'XMRV Testing, Treatment and Transmission' started by Marco, Dec 8, 2009.

  1. redo

    redo Senior Member

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    From nature:
    http://nature.com/bmt/journal/v31/n11/full/1704061a.html
    So... Rituximab can have a great effect on EBV.

    Quote from another study, about the whereabouts of EBV:
    What if B cells also were the principal reservoir for XMRV?
  2. redo

    redo Senior Member

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    Yes. Or the B-cells could produce proinflammatory cytokines or antibodies which work auto immune wise... And by wiping out the B-cells you also stop that process...

    Or, by wiping out the B-cells you would also wipe out the viruses inside the cells (such as we know for sure EBV can be, and we can speculate, with good reason, that XMRV could be in the same place...).

    Just a short note to those who follow this thread: this is a bit learn as we go. I am a layman like most others on this forum, and I in the process, of what I can read about the different monoclonal anitbodies, the diversity in how they work is BIG. Comparing two different ones is like comparing fish to oranges... They are both food, but that's it. And the various monoclonal antibodies are monoclonal and they are antibodies (like other antibodies in the body). But they are made so that they are specific antibodies....


    Rituximab (the monoclonal *antibody*) binds to the CD20 antigen. A antigen and a antibody = a immune complex. When the antibody meats the antigen, the B-cell often dies (cell lysis). This is how it works.

    The fact that it's monoclonal means that it is specific, cloned up...

    If you are new to this, then I recommend giving the wiki on this a few moments of your time: http://en.wikipedia.org/wiki/Monoclonal_antibodies
  3. redo

    redo Senior Member

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    This is a reply to posts on this thread.

    As I understand it. Apart from the small PML risk, the main difference is that they don't produce antibodies like normal, because the B cells are involved in antibody production. They take blood samples when they begin (first dose), and at the second dose, and sometime later in the treatment. They measure B cell level in the body, immuneglobulin levels, and some other things. They are not given any precautions.

    As I read it, here. "CD20 is expressed on mature B cells providing a target for MabThera. " It's not all b cells, but pretty much all (the mature ones, and once other ones mature, they become targets as well).

    The rituximab (which is a monoclonal antibody) binds to the CD20 antigen. The CD20 antigen is on the surface of b cells, so the cells die when the antibody meats the antigen. As I understand it, people will have high levels of Rituximab in the blood for some months after the infusion, so when new b cells try to form, they are met with the monoclonal antibody, and dies - and that's why it takes months and months until the levels of b-cells begin to rise again. Below the graph here, you can see numbers of CD19, the numbers of CD19 correlates with b cell levels in the body. As you can see, it takes some five months until they rise again (that's probably when the monoclonal antibodies from the rituximab has reached low levels).
  4. redo

    redo Senior Member

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    As we know, both Tysabri and Mabthera (Rituximab) are drugs which might give the patient PML. PML comes from the JC virus, a virus which 3/4 people have (latent), and which can flare up when the drugs Tysabri or Rituximab are given.

    I guess the PML risk is somewhat different when comparing those two drugs, but what they have in common is that in order for someone to get ill from the latent JC virus, the immune system must be 'challanged' for a while. PML is much more common in AIDS patients than in patients receiving some of these drugs.

    I just found this very interesting statement about PML risk in Tysabri.

    So it seems that the PML risk is something which comes after a year or more when using Tysabri...
  5. redo

    redo Senior Member

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    Here's an other mechanism which Rituximab may work through (just a hypothesis):


    An active viral infection, leads to a active disruption in the immune system. As long as we have a active disruption in the immune system (among other things), we get heavy symptoms.

    One could break that chain at any point (and get better), either treat the virus (directly or indirectly), or treat the immune imbalance, or use symptom allivating drugs (painkillers for pain etc)

    With HIV MCD they have used Rituximab, and that caused a steep decline in cytokine levels (which previously where markedly higher than normal). HIV MCD and XAND CFS (if it is such thing) are vastly different, but nevertheless I like seeing such a decline in the cytokine response. I personally think the cytokine response is a major reason why we feel ill.
  6. redo

    redo Senior Member

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  7. acer2000

    acer2000 Senior Member

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    The thing I worry about using drugs that directly block the action of the immune system is whether we wouldn't be trading short term gain for long term problems. If you knock out all your b-cells for a few months, perhaps you feel better because the cytokines go down, but if CFS is is a result of infection and the B cells are producing cytokines because they are holding back that infection you might be in trouble. Pure speculation, but something that has crossed my mind a few times.

    The other paradox here is why do some people feel better when infused with IVIG (antibodies) but people also feel better when they take Rituximab?

    Another monoclonal antibody I have been watching is called Bavituximab. It has broad spectrum anti-viral properties and is also being studied in cancer. Clinical trials are going on now with HIV+HCV co-infected patients.

    http://www.drugs.com/clinical_trials/peregrine-s-anti-viral-bavituximab-nature-medicine-6303.html
  8. redo

    redo Senior Member

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    Rituximab lowers HIV-1 count

    I read more from the study I mentioned in the post above, and it seems Rituximab lowered the HIV-1 count (I read the whole study, and coundn't find a word about ARVs).

    If you look at the scheme in the bottom there, you can see that it has gone down:

    http://bloodjournal.hematologylibrary.org/cgi/content/full/113/19/4521/T1

    I don't know if it's much or not, but the P-value is low, so I guess they are pretty certain it's not just a coincidence.
  9. redo

    redo Senior Member

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    Yes, that's a very valid point. What if the reason for the high levels of cytokines is the body trying to fight the infection (and not the infection trying to fight the immune system).

    When it comes to short term benefits traded for long term losses, I think MS is the closest thing to look to. There have been semi large studies on Rituximab and MS, one completed some years ago (Hauser).

    I think that group is in the clear. But if CFS patients would be, well I guess we have no way of knowing for sure. And that goes for MS as well (it's only a semi large study, and it hasn't gone that many years since it was completed).

    I have used IVIG myself, and I actually got a little worse from them. And noticed nothing else.

    As I understand it lowering antibody levels isn't the primary mechanism of which Rituximab works. I'd rather think of that as a "side effect".

    Keep us posted if you find any news on Bavituximab and CFS (or related conditions).
  10. redo

    redo Senior Member

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  11. redo

    redo Senior Member

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    Good news for those who are worried about the PML aspect of the treatment. A casse report shows that it may be stopped with an antimalarial drug:
    www.ncbi.nlm.nih.gov/pubmed/20562463
  12. Daffodil

    Daffodil Senior Member

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    they can get rid of the JC virus altogether with cidofovir + cytheris' IL-7 drug
  13. liquid sky

    liquid sky Senior Member

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    Do you have a source for this, Daffodil? I am considering this drug and the risk of PML is the biggest drawback. Kinda scares me.
  14. Daffodil

    Daffodil Senior Member

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  15. liquid sky

    liquid sky Senior Member

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    Thanks so much. I want to have the info on file if I decide to use the Rituxan. It is amazing what doctors do not know. My doctor told me they could use antibiotics for PML, then gave me a brochure about Rituxan that said there is nothing that can be used to treat PML. Confusing and still scary.
  16. redo

    redo Senior Member

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    Well, there's only case reports showing it can be cured. But that said, it's very rare, if never that people get PML within the first year of treatment. I think I wrote some about it above.

    Daffodil, great find!
  17. Cort

    Cort Phoenix Rising Founder

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    Update from Dr. Mella on the study

    The double-blinded, placebo controlled study of Rituximab is completed, the paper written and has been sent to a journal for publication (no word on its fate). The study was apparently successfu as he states

    'we are presenting strong indications of the mechanism behind this poorly understood entity to be autoimmune).

    The next study (NCT01156909) of Rituximab intervention and maintenance in 25 patients (giving the drug up to 14 months) is underway. This study has 3 years of follow-up, but they will try to publish an initial analysis after one year.
  18. liquid sky

    liquid sky Senior Member

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    Great news, Cort. I hope it gets published soon. I have believed that what they call auto-immunity is at work in ME. That doesn't eliminate the possibility of a pathogen being involved.

    If I remember right, the publishers were leaning towards either auto-immunity or a pathogen that lived in the B cells. I wonder if they have eliminated the latter conclusion?
  19. sensing progress

    sensing progress Senior Member

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    what the heck does that mean?
  20. serendipitycat

    serendipitycat

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    When?

    I'm just curious - how long do you think it will take before we see this published online or in a journal? Sometimes it takes months of peer-review, so... I want to see it now!! :-D

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