Copaxone another mechanism

Cortical excitability changes over time in progressive multiple sclerosis.Ayache SS, Créange A, Farhat WH, Zouari HG, Lesage C, Palm U, Abdellaoui M, Lefaucheur JP. Funct Neurol. 2015  25:1-8. [Epub ahead of print]

OBJECTIVE:Glatiramer acetate (GA; Copaxone), a disease-modifying therapy for multiple sclerosis (MS), promotes development of anti-inflammatory (M2, type II) monocytes that can direct differentiation of regulatory T cells. We investigated the innate immune signaling pathways that participate in GA-mediated M2 monocyte polarization.
METHODS: Monocytes were isolated from myeloid differentiation primary response gene 88 (MyD88)-deficient, Toll-IL-1 receptor domain-containing adaptor inducing interferon (IFN)-β (TRIF)-deficient, IFN-α/β receptor subunit 1 (IFNAR1)-deficient, and wild-type (WT) mice and human peripheral blood. GA-treated monocytes were stimulated with Toll-like receptor ligands, then evaluated for activation of kinases and transcription factors involved in innate immunity, and secretion of proinflammatory cytokines. GA-treated mice were evaluated for cytokine secretion and susceptibility to experimental autoimmune encephalomyelitis.
RESULTS: GA-mediated inhibition of proinflammatory cytokine production by monocytes occurred independently of MyD88 and nuclear factor-κB, but was blocked by TRIF deficiency. Furthermore, GA did not provide clinical benefit in TRIF-deficient mice. GA inhibited activation of p38 mitogen-activated protein kinase, an upstream regulator of activating transcription factor (ATF)-2, and c-Jun N-terminal kinase 1, which regulates IFN regulatory factor 3 (IRF3). Consequently, nuclear translocation of ATF-2 and IRF3, components of the IFN-β enhanceosome, was impaired. Consistent with these observations, GA inhibited production of IFN-β in vivo in WT mice, but did not modulate proinflammatory cytokine production by monocytes from IFNAR1-deficient mice.
CONCLUSION: Our results demonstrate that GA inhibits the type I IFN pathway in M2 polarization of monocytes independently of MyD88, providing an important mechanism connecting innate and adaptive immune modulation in GA therapy and valuable insight regarding its potential use with other MS treatments.

We like to publish the mechanism of action of drugs and copaxone gets a new one month on month. This time it inhibits an interferon pathway of inhibitory macrophage pathway and inhibited pro-inflammatory proteins it also inhibited beta interferon production in mice…but would this not be anti-inflammatory if beta interferon works….so long peeps can’t wait for the next one

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  • Bubonic plague in mice:)

    As Dustin Hoffman in Rain Man would say, "Definitely not climate change".

    BUT! There is hope! I expect global politicians to tell everyone to make ice cubes all over the globe and throw them on their lawns.

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    Just have to recognize how they interpret terminology and the entire world makes sense.

  • Copaxone was developed with the EAE model. Since it is junk and NICE has determined in it's infinite wisdom it is useless, the same can be said of EAE and the whole EAE academic industry.

    • I think Copaxone was developed in an era when science was actually trying to cure a disease. Maybe they should have focused on immunosupprsants right off the bat?

    • i think you will find that if you compare apples with apples then the efficacy in animals is not incosistent with efficacy in humans how many eae studies can you find where they inject animals after an attack starts and inject it under the skin not with an adjuvant.

      This is your task find that paper and we can review it. but i may have missed it.

      ps this sells ovet four billion a year so not bad for so called junk should we be binning neurologists as animals non human at least are not doing the prescription

    • I think no one can argue that Copaxone is inferior when it comes to halting relapses in a 2 year trial when compared to just suppressing your immune system. This is especially true since it has been said that it takes 6 months before it takes full effect.

      But beyond the 2 year trial, how does it change your system? These are the questions that many of these researchers are trying to understand. This is quite different than studying immunosuppressive agents since the MOA is a no brainer.

    • If your are NEDA it is not worthless indeed.

      No on can argue it is inferior when looking at relapses in a 2 year trial….I think you can argue where is your data t support there are not things better

    • Sorry, what I meant to say it is obviously inferior in terms of reducing relapse rate in a 2 year trial to the immunosuppressive drugs. But for long-term efficacy I guess there is no definite way of proving it's usefulness oher than the longterm follow-up studies which are pop poo'd by Team G, or anecdotes of which I can attest to.

      So I think research is still being undertaken after 20 years to figure out what is its MOA as it seems to be unique compared the obvious immunosuppressive action that most new therapies rely on.

    • I am happy this is a long-term success story, but likewise for the success we could also hear a failure.

      Long term studies are not poo pooed bring them on if they are dont properly

      I think much of this research ifor MOA is part of the marketing strategy to keep the compound in the eyes of the public and neurologists. How much of this is truely independent of Teva?

      Should do a review of the data.

      Has anyone found the paper(s) I asked for yet?

    • I don't understand what papers you are asking for. Are you looking for papers where Copaxone stopped an EAE attack that was already initiated? If this is the case I think there are no studies that showed this.

      Again, Copaxone does not seem to act as fast as a immunosuppressant so I would not expect it to instantly shut down an auto-immune response

    • Yes stopping an relapsing attack after the first one has happened with subcutaneous glatiramer. Where is the paper? You don't think there is one. Teva Reps any ideas?

      Animal studies were supposed to be the reason why Copaxone was developed, so now we are saying really that it takes so long to work in humans that it could not possibly work in animals. So why blame animal studies for anything that happens in humans?

    • I guess the point is if you are just strictly looking at halting all disease activity as fast as possible such as an EAE experiment, total body irradiation would be the best solution.

      But I think the scientists who discovered Copaxone were trying to find a way to inducelebrate EAE and instead found a compound that reduces the severity.

      How this translates to humans is why other scientists are still interested in discovering how it works and gaining further insight into the disease itself. For others, the EAE model is used to evaluate how fast an immnosupressant stops disease activity. This is ideal when taking it to a 2 year trial but has no longterm bearing on the course of the disease.

  • Hey I even like that Copaxone was this whole panacea, because I'm in treatment with him, but I know what the "real world" … Teva is funding these studies ?! May only…

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