Thursday, 2 February 2017

Newsflash. Major target for treatment of MS

#MSresearch, How to treat #MS!


Aetiology, Pathology and Treatment Converge


MAJOR TARGET FOR 
TREATMENT OF MS



CoI: Me None. ProfG & DrK multiple

43 comments:

  1. Thank you for making this available for free.

    And hey, I didn't have to wait for 24 hours!

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  2. Well done everyone! And thank you very much for all the hard work.

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  3. Please tell me that this is this related to EBV?

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    1. Memory B cells are those that get infected by EBV.

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    2. Remove the memory B cell and you remove EBV

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    3. Am I interpreting the data correcting in inferring that a target of CD22 is the most "precise" course? would this hit the memory B cells without disrupting other processes?

      If so, are there any treatments in development along these lines?

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    4. Yes It is one possibility, there are a number of others

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  4. Hey! Congratulations all :-)
    especially MD #gettingstuffpublished

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  5. What these results mean in context of virus/autoimune hypothesys of MS deseas?

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    1. That is really cool!

      Have a unrelated question - how would you explain other autoimmune diseases with your hypothesis of memory B cells like psoriasis?

      cos I have both MS and psoriasis.

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    2. The simplest suggestion is that it is the same mechanism EBV related B memory cells some CNS directed others into the skin

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    3. If one looks through the literature I can find evidence from arthritis, lupus, nephritis, NMO and more to support this view.

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    4. Thanks Mouse.

      But how would you explain the fact that I first got psoriasis at 4 years of age and years later at 31 got MS?

      I must have got infected with EBV as a toddler?

      And why came the skin first?

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    5. I'll have a think, but should we think about type I diabetes into the argument as an autoimmune disease,but to suggest early EBV infection may not be outside the realms of reality.

      https://www.ncbi.nlm.nih.gov/pubmed/23868878
      "The prevalence......by age group was as follows: 6-8 years, 50%; 9-11 years, 55%; 12-14 years, 59%; 15-17 years, 69%; and 18-19 years, 89%."

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    6. The view of the paper is that memory B cells are a central issue. They will be there shortly after birth as you immune system matures.

      If the memory B cell is the central player, We would need to understand what it is doing.

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  6. What does MrT think?
    Scientists looking at a cup of T

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  7. The reduction of peripheral memory B-cell reduces the attacks in RRMS. How does this affect the memory B-cells inside the CNS in meningeal follicles? Will reduction of memory B-cells in the periphery result in: plasma B-cell Ab reduction, clearance of OCBs and reduce neurodegenerative processes in progressive MS?

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    1. Reduction of memory reduces attacks? Is this cause or effect? During attacks memory cellls appear to drop.How does this affect follicles I dont know?

      Will reduction of memory cells result in clearance of OCBS and reduce neurodegenerative process. The data shows that drugs like alemtzumab that reduce peipheral B, do not reduce OCB.

      Ocrelizumab reduce peripheral B does this inhibit neurodegenerative effect and is this the reasons for influence on PPMS, I'm not convinced it is simply not an issue of inhibiting active disease.

      Mpost of the peripheral B cell depletors do not touch cells within the CNS

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  8. I thanked you already (but that was when I scanned rather than read the paper). Now that I've actually read it: wow, you've really gone all out. Thank you again.

    Do you expect that your colleagues will agree with your conclusions?

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    1. Will Colleagues agree?

      I suspect not, given the referees views we got. They were disbelievers but at least were willing for the opinion to surface. My point would be that the data is there and this demands debate...not blind faith.

      As you can see, I am a T cell fan and go some way to get them out of Jail, becuase the T cell inhibition of MS is pretty weak.

      Read the data and then find critism. Read the data and embrace what it says and see if it can make improvement?

      This is why we decided to put the data in figure 4 in the paper. (we had to pay for the pleasure) Look at it and then say is it all crap or is there something in it. If we simply used the references people would not read them and this would allow them to dismiss a contuary view without thought. Look at the data, it is in your face.

      There are lots of implications from the views given.

      Some we may be able to address, if we can get the data. Pfizer refused access to the data from anti-BAFF trial.
      Why?
      Did it make MS worse? Were they trying to protect their product in development in Lupus? I am a total fan of full access to trial data. It sttops pharma hiding stuff they don't waant you to see.

      We hope that people will take the time to read the paper, it challenges dogma, but does not say it is wrong but we should not accept the dogma or twist the data to fit the dogma as this can be disasterous as we will see when the next paper in this series materialises:-)

      Will people ask? Do we need CD20 treatment as often is proposed? Will we get a backbone and question?

      p.s. Thanks for your kind words. Thanks for reading the paper

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    2. Questioning whether some people are being overdosed by Ocrelizumab in a paper you are publishing was one (of a number) of reasons for the WOW - I was thoroughly and genuinely impressed.

      I had read echos of 'could ocrelizumab be an induction treatment' on this blog, but publishing a paper questioning the issue (for the explained) is impressive.

      What is your theory on the connection between the number of memory b cells entering the CNS and the severity of MS?


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    3. ... and by extension, one efficacy of dmt relative to the extent of the Dmt related decrease in the number of memory B cells entering the CNS?

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    4. Yes that is a potential interest that influence of efficacy creates a hierarchy of efficacy of treatment. It is not far off this.

      However we have to accept there may be multiple actions of the different agents

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    5. Theory on coƱection of B cells and severity... A hard on that I have yet to get my head round. If B cells produce antibody they can indirectly stimulate microglia via virtue of their FC receptors this would mean the specificity of antibody is unimportant and maybe a reason why a consistent autoantigen has not been found

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    6. thank you. i'm grateful for your thinking.

      i should have clarified that my question re severity of MS and efficacy of dmts was in the context of realpses/new lesions - not disability. but you've impressed me so much i'm willing to patiently wait without frustration for at least 12 months ;)

      thank you again, your bravery made my day.

      ps. your bravery may have made my day from a theoretical point of view, but imagine what it's doing for my partner and her oncologists to be able to consider lesser ocrelizumab/rituxaimb dosing then an indefinitive redosing at every 6 months - frankly it makes a huge difference.

      i know it's all theories etc and a lot of it is unknown: but that's ok, the known options are pretty bleak too lol ;)

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    7. Thanks OK I was thinking you were talking about relapses/lesions. I can assure you you won't need to wait 12 months to get more meat on the bone.

      More Bravery to come ....Gulp

      In the oncology field it is important to ask the question which type of B cell is the problem, because some of the B cell sub populations recover very quickly and this could determine the frequency of dosing. I will do a post on this.

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    8. P.S. It is not brave of me.....ProfG and the other neuros will take the flak...I wonder when their phones will start ringing.

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    9. Concerned of Tunbridge WellsFriday, February 03, 2017 9:53:00 pm

      Mouse Doctor "a hard on that I have yet to get my head round". I'd prefer if you stuck to the MS research rather than this sordid stuff. I'm sure Prof G would suggest that you cut back on the viagra. No more filth please.

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    10. Sorry see below, hope you had a laugh at least

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  9. Sorry predictive text problem That is a hard one to answer

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    1. I was thinking, that's too much information!! ;-)

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  10. MD and the rest of you wonderful bloggers. I'm a very tired mum of a new baby and I am very excited about the news about causes of MS. My tired brain cannot fathom if this holds true for PPMS,especially if there is no active disease and the damage is from previous lesions etc.
    Any thoughts?

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    1. there is nothing in the mode of operation of ocrelizumab that suggests it would reverse disability/symptoms caused directly by long standing lesions.

      ps. i'm venturing a guess, i'm not a scientist or a doctor

      if your CNS is very very inflammed (and MRIs can be a poor predictor of the existence of inflammation) and you have treatment that reduces the inflammation, you may find your functional levels improving: they suspect due to reduction in inflammation of CNS, your system is more able to re-route and have a greater functional reserve then if it is inflammed. kind of like when your finger is inflammed and you find hard to move or bend it until the inflammation goes down

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  11. What a paper, congrats to Barts MS group.

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  12. I just loved this post, Congratulations!

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  13. Ahem, just to mention the typo in the Abstract: interestingly.

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    1. tell me about it, we requested it to be changed to "of interest"

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