Wednesday, 4 November 2015

And now for some more B cell action

Ireland SJ et al.  The effect of glatiramer acetate therapy on functional properties of B cells from patients with relapsing-remittingmultiple sclerosis.JAMA Neurol. 2014 Nov;71(11):1421-8. doi: 10.1001/jamaneurol.2014.1472.

IMPORTANCE: This study describes what is, to our knowledge, the previously unknown effect of glatiramer acetate therapy on B cells in patients with relapsing-remitting multiple sclerosis (MS).
OBJECTIVE:To determine whether glatiramer acetate therapy normalizes dysregulated B-cell proliferation and cytokine production in patients with MS.
DESIGN, SETTING, AND PARTICIPANTS: Twenty-two patients with MS who were receiving glatiramer acetate therapy and 22 treatment-naive patients with MS were recruited at The University of Texas Southwestern Medical Center MS clinic. Cell samples from healthy donors were obtained from HemaCare (Van Nuys, California) or Carter Blood Bank (Dallas, Texas). Treatment-naive patients with MS had not received any disease-modifying therapies for at least 3 months before the study.
EXPOSURES:
Glatiramer acetate therapy for at least 3 months at the time of the study.
MAIN OUTCOMES AND MEASURES:B-cell phenotype and proliferation and immunoglobulin and cytokine secretion.
RESULTS:A restoration of interleukin 10 production by peripheral B cells was observed in patients undergoing glatiramer acetate therapy as well as a significant reduction of interleukin 6 production in a subset of patients who received therapy for less than 32 months. Furthermore, proliferation in response to high-dose CD40L was altered and immunoglobulin production was elevated in in vitro-activated B cells obtained from patients who received glatiramer acetate.
CONCLUSIONS AND RELEVANCE:Glatiramer acetate therapy remodels the composition of the B-cell compartment and influences cytokine secretion and immunoglobulin production. These data suggest that glatiramer acetate therapy affects several aspects of dysregulated B-cell function in MS that may contribute to the therapeutic mechanisms of glatiramer acetate.


You know how we like to give Glaterimer a new mechanism of action every now and them. It was said that Copaxone will be shown to stop B cell activity as anti-CD20 comes to market. 
So someone nudged me to say its already here and that we (TeamG) are late coming to the B cell show and sent this little gem. 
Well I would say this is not exactly true and when you see ocreluzimab in bright lights and our EAE data you may find out more.

7 comments:

  1. Team G Is EAE, T cells, Tysabri, EBV, Cladribine, neuro-protection. We have Prof Hauser and other groups to thank for B cell research. Team G is good, but jumping on the B cell bandwagon looks like you were slow on the uptake.

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    1. We cannot do every thing, and we moved our fon-clinical science focus away from immunology a long time ago because of unmet need.. However you are presumptuous about what we do and do not do. I started in a lab on B cell regulatory cells...tbut that view was killed by the American CD8 T suppressor cell mafia. B regs will be a hot topic

      Now whilst I am on a high horse and I am not trying to belittle the work that Prof Hauser has done has he has indeed flown the MS flag, however the idea of anti CD20 depletion to treat autoimmunity has a much longer history that in MS.

      If you take the cynical view then this was just something obvious to do based on what was shown many years earlier in arthrtis. Just as Alemtuzumab did not have its history in MS either. Indeed I remember seeing it on the news when a London group first started doing this stuff of anti B cells treatment probably in the 1990s.

      There are few truely original ideas and much of MS is jumping on the bandwagon of other science. Microbiome, genone mapping T regs, stem cells etc etc etc. However the idea of anti-CD20 depletion for arthritis has been dropped because of safety worries, but in MS you as a population are willing to accept more risks.

      Last year we saw vegal nerve stimulation for atreatment rthritis when will it occur in MS?
      So remember this when you start to wag your finger

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    2. Glatiramer Acetate seems to be the wonder drug! I think Team G is upset that they didn't get in on the ground floor and bought Teva stock back in the 90's.

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    3. Don't you mean 70's.

      To buy stock you need spare cash or a love of oxo:-)

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  2. Hi MouseDoctor, I am new to this wonderful website. Does it really matter about how Copaxone works? Overall, in trials, it has a marginal decrease in relapses (30% above placebo) and no proven effect on disability progression. This drug is well past it's expiry date. If we are looking at MS, in terms of NEDA or disability progression, it fails miserably. It seems Teva is trying to jump on the B-cell bandwagon to appear relevant in this new age of much more efficacious MS medications. I am surprised this was published in JAMA neurology.

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  3. I think Nissan Grifter must be a Biogen sales rep. who is worried about loosing his job due to the Tecfedera sales slump. Also the realization the Natiluzimab has zero effect on brain atrophy can't be good for his future employment prospects either.

    It's amazing that 20 years after the introduction of Copaxone, the best Pharma can do is market immunosuppressive drugs that put you at risk of PML and are contradictated for use while pregnant. Hello Pharma, you should look into who your target patient population is!

    It's no wonder people are opting to still use Copaxone over the "highly effective" therapies despite the NEDA marketing strategy.

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