The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
Simon McGrath concludes his blog about the remarkable Prof George Davey Smith's smart ideas for understanding diseases, which may soon be applied to ME/CFS.
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Alternatives which work like Rituxan

Discussion in 'Rituximab: News and Research' started by kms1990, Dec 16, 2016.

  1. kms1990

    kms1990

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    Hello,

    This is one of my first posts, and I am relatively new to the site. (or at least newly interested in the board).

    It would be great if there was a thread of ideas for alternatives to Rituxan. (both serious RX meds and alternatives)

    I think that requirements for an idea would be that the alternatives have to work on the assumption that CFS / Dysautonomia is a form of autoimmune illness that mainly effects the Alpha / Beta and Muscarinic receptors throughout the body and possible effects even more receptors or tissues that have not yet been defined. (OR AT LEAST A SUBSET OF CFS)

    The ideas I have heard so far are (updated 12.17.16):

    1) High dose IVIG: The theory is this suppresses the bodies own production of antibodies because there is already a high amount of immunoglobulins in the blood. (I dont think this is proven how this works just a guess). Without the offending antibody production the body can then function without these receptor antibodies.

    2) Plasma Exchange: The theory is this removes the offending antibodies form the body (along with all other antibodies in the blood stream). Without the offending antibody production the body can then function without these receptor antibodies.

    3) Rituxan: The theory is this antibody drug depletes B cells which may be creating or signaling to create the receptor antibodies in question. Without the offending antibody production the body can then function without these receptor antibodies.

    4) Peptide (peptidomimetic) Therapy: The theory here is to interrupt the function of these auto antibodies so they no longer have the same impact on the receptors in question. Without the offending antibodies ability to impact their previous targets the body can then function without these receptors being activated or suppressed.
    Related Peptide Studies:
    https://www.ncbi.nlm.nih.gov/pubmed/25691619
    https://www.ncbi.nlm.nih.gov/pubmed/26446828

    5) Cyclophosphamide: The theory is this drug targets B cells which may be creating or signaling to create the receptor antibodies in question. Without the offending antibody production the body can then function without these receptor antibodies.

    6) Azathioprine:
    Suppresses lymphocytes production from bone marrow. T and B cells are particularly affected. When B cells are decreased there may then be less of them to produce or signal to produce the offending antibodies.

    7) Steroids:
    In theory would suppress but not reverse an autoimmune state. There then may be less offending antibodies to the receptors in question.

    8) Belimumab:
    In theory belimumab would suppress but not reverse an autoimmune state. It may have the disadvantage of tending to induce suicide in the B cells that are not doing much anyway - which is what steroids do. It does not work for RA but works for lupus at least in the short term. It is certainly a possible alternative but less easy to predict what it would do.

    Are there any other ideas out there on what might help suppress these auto antibodies from being produced at high levels?
     
    Last edited: Dec 17, 2016
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  2. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    The Norwegians have been trying cyclophosphamide, which targets B cells. I have reservations about this because we had largely given up using it in other autoimmune diseases because of toxicity. However, each condition may be different in terms of risk/benefit for individual drugs. The neurologists use steroids and azathioprine to reduce antibody levels. This was never a very satisfactory strategy for rheumatoid arthritis, although it was of some value for lupus and myositis cases. Like cyclophosphamide, azathioprine has worries about long term cancer risk.

    The next stage should be to try to find treatments that target just bad B cells. There have been some attempts at this but it is very early days. The added problem for ME is that we do not know how many if any patients really have relevant autoantibodies. It is by no means clear that they are to adrenergic or muscarinic ACh receptors even if they do exist.
     
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  3. Gingergrrl

    Gingergrrl Senior Member

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    @kms1990 I have not heard of Peptide Therapy but am very familiar with all of the other treatments that you posted. I was curious where you heard of it for reducing/eliminating autoantibodies?

    I clicked on your links but they are about rabbit studies. Has this Tx been used in human studies and can you explain it to someone like me who is scientifically impaired?

    The only other things I have heard are Cyclo, steroids and immunosuppressants, like Imuran or Cell Cept, like Dr. Edwards mentioned below.

    @Jonathan Edwards I have heard the same things re: cancer risk with Cyclo and Imuran which is why I am not pursuing those at all and I think are risky for anyone with Auto Abs that correlate with paraneoplastic syndromes.

    Re: your second point, are there treatments that target just the "bad" B cells and leave the others intact?!! What are those kind of treatments called?!!

    Re: your last point, some of us (like me) have proven auto antibodies to beta adrenergic and anti muscsrinic receptors but whether this means we have ME is another issue IMO. I am viewing my treatment as targeting the Auto Abs regardless what my illness is ultimately called.
     
  4. kms1990

    kms1990

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    @Gingergrrl , unfortunately, these are very very preliminary and to my knowledge only have been done in animal studies. You will see from those studies they only target some of the auto antibodies in question so they are not even covering all the auto antibodies that may be in play with this illness. I learned about these from a presentation I watched by Dr Kem. (). The presentation is very interesting. I believe he is trying to develop these peptides to block the function of these auto antibodies. Imagine how great this type of theraphy could potentially be for a disease like myasthenia gravis as well.

    One hopefully thing to note, is that I believe he or doctors he has worked with have treated patients with immunomodulating therapys with success. A very well known POTS doctor from NY who initially dx me with POTS years ago told me he might be the best person to speak with once my celltrend labs turned up positive.
     
    Last edited: Dec 16, 2016
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  5. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    They are at a very early stage of research. The idea is to get cytotoxic cells to knock out bad B cells with the help of targeting antibodies. Whether it will work in clinical practice is very uncertain so far.
     
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  6. Gingergrrl

    Gingergrrl Senior Member

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    Thanks and I watched a presentation a few months ago with Dr. Kem re: IVIG which was very interesting. Will bookmark that post so I can watch it later from home and we'll keep sharing info by PM, too. Am curious which Auto Abs these peptides target?!!

    It would be amazing and I think I actually have heard about this before but did not realize it was called Peptide Therapy. Am tagging @halcyon and was curious if this is the same thing he was once telling me about re: Dr. Kem developing for future treatments?

    Will definitely have to get more info on this from you (and apologies if you already told me)!

    Wow, this sounds very exciting! How far along are they in the research process?!
     
    Last edited: Dec 16, 2016
  7. halcyon

    halcyon Senior Member

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    Yup, same thing.
     
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  8. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I am fairly sceptical about this option. I cannot see how it could be turned into a practical long term therapy for human illnesses and the immunology looks a bit simplistic. The reports seem to come only from one group and are published in a very obscure journal. Similar ideas for using blocking mimetic compounds have been around for about thirty years and never seem to have got further than early animal data.
     
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  9. Thinktank

    Thinktank Senior Member

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    @Jonathan Edwards , i wonder if belimumab might be an option? If i understand it very basicly It prevents the binding of BLyS, which then causes b-cell suicide.
     
  10. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    At least in theory belimumab would suppress but not reverse an autoimmune state. It may have the disadvantage of tending to induce suicide in the B cells that are not doing much anyway - which is what steroids do. It does not work for RA but works for lupus at least in the short term. It is certainly a possible alternative but less easy to predict what it would do. I doubt it would induce long term remission in the way rituximab does in some conditions.
     
  11. Jenny TipsforME

    Jenny TipsforME Senior Member

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    Would myasthenia gravis meds be useful to us? Or is this targeting the wrong type of AchR?
     
  12. kms1990

    kms1990

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    I think in certain cases the answer would be yes. My old POTS doc who is an expert in dysautonomia said "If there is reduced cholinergic activity, I might consider mestinon (pyridostigmine)". However, I think this is really case by case and also dependent on which antibodies you have.
     
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  13. kms1990

    kms1990

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    @Jonathan Edwards yes it does look very preliminary. However, look at the distribution of pubmed articles which include
    Peptidomimetic! this is a growing area of interest in general. Maybe technology is advancing to a point where this type or targeted therapy will be possible in the future.

    upload_2016-12-17_11-45-33.png
     
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  14. Gingergrrl

    Gingergrrl Senior Member

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    @halcyon thank you for clarifying and refreshing my memory on this one!

    @Jonathan Edwards Are you skeptical just of these preliminary animal studies or also of the medication that Dr. David Kem's group is working on that involves a Peptide compound (not sure if compound is the correct word)?!

    Jenny, in my own case, the MG meds did not work and I had a horrible reaction back in 2014 to just 1/8 of a Mestinon.

    I was told that my auto antibodies are to the muscarinic receptors (vs. the nicotinic receptors in MG). Both are cholinergic but two different types. This is about the extent where my knowledge stops! Hoping someone else can explain it better than I can!
     
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  15. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    @Jonathan Edwards my main reservation with cyclo is that as far as i understand it can thwart bone marrow function, did any of your patients get side effects in that relation? Or "cancer-fatigue" after?
     
  16. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Trendiness, as judged by number of publications, is usually a sign of a blind alley in biomedical science. The rise in publications probably just reflects fashion and maybe cheap peptide synthesisers. The basic idea seems to me unlikely to ever be much use. Antibodies do not normally bind to peptides. They bind to whole proteins. Peptides are for T cells. Simple mistakes like that have become the norm in immunology I am afraid.
     
  17. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Bone marrow suppression at the doses likely to be used is not a big issue. I am not sure what candcer fatigue would be if we are talking about a side effect of a drug. For most people the real problem is that it makes you horribly sick.
     
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  18. kms1990

    kms1990

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    Ah darn! That is too bad!
     
  19. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I am sceptical of a peptide being any use for a real human illness. The overall dynamics do not make sense to me - by which I mean it is a bit like cooking a dozen sausages one at a time. You would end up with eleven cold sausages on your plate.
     
  20. Gingergrrl

    Gingergrrl Senior Member

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    Thanks and was just curious. I have not researched this at all and don't know enough yet to really have an opinion.

    Is the concept that the autoantibodies would bind to or attack the Peptide instead of the person's receptors/body?
     

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