Glatiramer works by targeting the mechansism responsible for MS

G

The FDA label says “

The mechanism(s) by which glatiramer acetate exerts its effects in patients with MS are not fully understood. However, glatiramer acetate is thought to act by modifying immune processes that are believed to be responsible for the pathogenesis of MS.

These processes has changed over time so this paper made me smile

Here, they show that GA treatment revives antiviral T-cell responses and determines a shift in B-cell phenotypic distribution with an increase of naive and a reduction of memory cells.

However how well does it do the job? Because what ever it does it has to reflect how good it works in MS. I would say with the B memory cells it is just about right

Figure 5

Gisella Guerrera, Serena Ruggieri, Mario Picozza, Eleonora Piras, Francesca Gargano, Roberta Placido, Claudio Gasperini, Marco Salvetti, Maria Chiara Buscarinu, Luca Battistini, Giovanna Borsellino, Daniela F. AngeliniEBV-specific CD8 T lymphocytes and B cells during glatiramer acetate therapy in patients with MS Neurol Neuroimmunol Neuroinflamm Nov 2020, 7 (6) e876; DOI: 10.1212/NXI.0000000000000876

Objective Infection with Epstein-Barr virus (EBV) has been associated with clinical activity and risk of developing MS. The purpose of this study is to investigate the impact of glatiramer acetate (GA) therapy on EBV-specific immune responses and disease course.

Methods We characterized EBV-specific CD8 T lymphocytes and B cells during disease-modifying treatments in 2 groups of patients with MS. We designed a 2-pronged approach consisting of a cross-sectional study (39 untreated patients, 38 patients who had undergone 12 months of GA treatment, and 48 healthy donors compatible for age and sex with the patients with MS) and a 12-month longitudinal study (35 patients treated with GA). CD8 EBV-specific T cells and B lymphocytes were studied using pentamers and multiparametric flow cytometry.

Results We find that treatment with GA enhances viral recognition by inducing an increased number of circulating virus-specific CD8 T cells (p = 0.0043) and by relieving their features of exhaustion (p = 0.0053) and senescence (p < 0.0001, p = 0.0001). B cells, phenotypically and numerically tracked along the 1-year follow-up study, show a steady decrease in memory B-cell frequencies (p = 0.025), paralleled by an increase of the naive B subset.

Conclusion GA therapy acts as a disease-modifying therapy restoring homeostasis in the immune system, including anti-EBV responses

About the author

MouseDoctor

23 comments

  • I have been on Daily Copaxone then generic Glatopa since diagnosed 12 years after first episode hemibody numbness, then optic neuritis episode then another hemibody numbness episode before being diagnosed . I was on CombiRx study randomized to Copaxone arm. No exacerbations since 2007. Dr. Panitch was my Doctor who said it was a decoy. Lately had a few doubters poo pooing Dr. Panitch and Copaxone. This study makes me feel better. I figured it must still be effective because it costs so d*mn much. Luckily I have good insurance. BTW, I thought it was similar to bee sting therapy. I met the bee sting man and his wife in Burlington, Vermont while working on neurology floor.

  • I’m sorry mouse, but isn’t this reminiscent of teriflunomide mechanism of action? Ie. can’t account fir why it is effective, so it’s anti ebv, etc.

    • 🙂 As it says it targets the mechanism important for MS, so if you say memory B cells are important it has to be shown to do this, EBV is important it has to do this, T regs are important it has to do this.

  • Not sure of the science behind it, but I (male, aged 57) was on GA for 19 years. I probably had disease signs up to 8 years before that (optic neuritis) but my official diagnosis came in 2000. During the GA years I had very few relapses and only early in those years. I am still high functioning with right side issues, mainly localized pain and foot drop. Late last year, being concerned with a continuing slow decline, my MS doc and I decided that I should give Ocrevus a try with the hope of slowing and possibly halting the decline. (I am VERY JC positive, so I’m afraid of Tysabri.) My doc said to give it a year before making any judgments, and it will be a year next month, and I can honestly say that I have gotten significantly worse this last year than the past 10 and I regret ever coming off of GA. I’ve heard and I believe that GA has a cumulative effect in the sense that the longer you are on it, the more effective it is and I tend to concur. Unfortunately for me, I’ve probably lost the advantage of those 19 years if I choose to back on it again.

    • Steve – sorry to hear about your experience. I have previously commented on my experience with Ocrevus (i.e. adverse reactions). However, I can say my second year on the drug was better than the first. It is not talked about much on the Ocrevus discussion boards, but initially feeling worse seems to be a common experience. Keep an eye out for adverse infusion related reactions, since it seems individuals that feel worse on the drug tend to report higher rates of adverse reactions. I had to stop after my fourth infusion.

      • Tom – So you’re saying that your infusions went fine until they didn’t? I can’t say that I’ve had any adverse reactions and I’m not sure I would know if I did. I assume you mean like post-infusion sickness, heart rate issues, etc. Correct? I’ve had a total of four infusions, the first pair at start, my 6 month and then my 1 year with all being unremarkable as far as what I would call infusion reactions. I just feel that over the past year, my foot drop has gotten worse to the point I’m considering a cane just to prevent falling on my face. A year ago, I would have believed that that consideration was several years down the road. I don’t know if I’m willing to hang in there for another year. MS sucks.

        • Steve – I agree, MS does suck, but at least it keeps life interesting. I am only three years in (well 3 years since my first major flair up, who knows how long I had MS before that) and have accepted I now need the support of a cane from time to time. For some insights to my infusion related reactions, see my comments under the 8/14/2020 post titled “A False Sense of Security”. The research discussed on this blog would suggest your b-cells should remain depleted for at least 12-18 months post last infusion, so you have some time to decide.

  • Glad to see people across the globe are finally looking for the right things.

    “Thus, it is conceivable that during disease activity, EBV reactivation is taking place, finding a weakened and senescent antigen-specific T-cell population, which is unable to contrast the viral infection.”

    If true, it would offer an easy to manage entry point to control the disease in the long run. I know valaciclovir didn’t show significant positve results in MS studies, but it seems to be effective against EBV reactivation nontheless, e.g.:
    https://jvi.asm.org/content/83/22/11857
    https://europepmc.org/article/med/15235312

    Wouldn’t it make sense to prescribe valaciclovir administration right before and continuously after a single anti-CD20 dose? That way you get rid of infected, malfunctioning or weak b-cells and t-cells and limit EBV reactivation before and afterwards, so the virus won’t reinfect those cells. That could make repeated anti-CD20 therapy unnecessary.

    And if the study findings are indeed true, additionally GA could become interesting in the aftercare to an anti-CD20 dose, to potentially break the devil’s circle.

  • In summary, all drugs that have been shown to work (some better, some worse) against MS are directly or indirectly anti-EBV … Maybe that’s a clue for something.

    • It seems that we ,I.e. MS research community, are avoiding the 800 lb gorilla in the room. We dance around the concept of EBV and dysregulation of the immunological response. Instead the focus in downstream lymphocyte activity. Address the cause of immune activation.

        • If you’ve followed this blog over the years, you will be in no doubt as to where the Mouse Doctors stand on Copaxone 😉

          • I know. I had to unsubscribe. You won’t have to answer my questions anymore. This disease in humans like myself is complicated by our life experiences, Trust in our Doctors, Hope. Mice 🐁 are easier to study. They don’t ask questions or feel old. Thanks for your honesty. Guess I thought this article had positive vibes for my Daily shots. Or even if it did, it’s too old school. Best Wishes Mouse 🐁 👨‍⚕️ 1️⃣

          • Sorry that you feel you need to unsubscribe…come back soon you can dip your toe in any time you feel like it. It probably does have positive vibes but I think it shows that it does not have major effects on B cells and this is why the efficacy on relapsing MS is on average weak. In my minde it was generated on a false logic. My experience with working with it in mice is that it works fantastically well when you mix the stuff into the innoculuum. It stops disease from developing, however give it under the skin after sensitization and it does nothing in mice. I must publish this sometime, over the years we have done the experiment a number of times and get the same answer. There are a few labs that have the midas touch in EAE, I sadly don’t trust their work.

          • Thanks for clarifying your position more specifically. I’ll be back 🐁
            At 62 I cannot imagine changing drugs even though I hear about all the new and improved drugs.
            The old nurse in me is constantly looking for answers. I appreciate your time.

          • Further more, what is evident in the CRAB drugs is that there is a range or responses some people are in the range of anti-B cell responses which is as good as potent DMT however more are not so if you are one of those individuals then that is great

          • Thanks so much. I almost said that. My disease is relatively mild in the spectrum of age of onset, level of Physical disability. Still I am smoldering a bit. Compared to no CRAB 🦀 drugs not even available when I took care of MS patients in 1982, it was a vast improvement over nothing then intermittent HD IV steroids. Always Wondered also about my bad case of mononucleosis in college, 1976, They put me on 80 mg prednisone Po on an 8 day taper. And genetically, my own unique immune system. Best wishes 🐁👨‍⚕️

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