The MS removal patch. Antigen-specific therapy works in Trial

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Epub: Walczak et al. Transdermal Application of Myelin Peptides in Multiple Sclerosis Treatment. JAMA Neurol. 2013 Jul 1:1-6. doi: 10.1001/jamaneurol.2013.3022.

IMPORTANCE: Demonstration of efficacious antigen-specific therapy in multiple sclerosis.

OBJECTIVE: To assess the safety and efficacy of transdermally applied myelin peptides in patients with relapsing-remitting multiple sclerosis. DESIGN One-year double-blind, placebo-controlled cohort study.

PARTICIPANTS: Thirty outpatients aged 18 to 55 years with relapsing-remitting multiple sclerosis. 


INTERVENTION: Skin patch with a mixture of 3 myelin peptides, MBP85-99, MOG35-55, and PLP139-155.

MAIN OUTCOMES AND MEASURES: Cumulative number of active gadolinium-enhanced (Gd+) lesions per patient per scan, mean volume of Gd+ lesions, cumulative number of new T2 lesions, and T2 lesion and T1 lesion volume change from baseline to the end of the study. Total number of relapses during the year of the study per patient (annual relapse rate), proportion of relapse-free patients, and proportion of patients with 3 months of confirmed disability worsening on the Expanded Disability Status Scale at month 12.

RESULTS: All patients completed the study. Compared with placebo, treatment with a myelin peptide skin patch (1 mg) showed a 66.5% reduction in the cumulative number of Gd+ lesions (P = .02) during the 12 months of the study. The annual relapse rate in patients treated with a mixture of myelin peptides (1 mg) was significantly lower compared with the placebo group (0.43 vs 1.4; P = .007). Treatment with a myelin peptide skin patch was well tolerated and no serious adverse events were reported.

CONCLUSIONS AND RELEVANCE: In patients with relapsing-remitting multiple sclerosis, treatment with a myelin peptide skin patch significantly reduced both magnetic resonance imaging and clinically defined measures of disease activity and was safe and well tolerated.




The aim of antigen-specific therapy is to reduce the immune response specifically so it only removes the the disease causing cells and so has no major side-effects compared to removing large parts of the immune system. The results are pretty impressive. They took three peptides that induce EAE in mice and humans can give T cell response to these peptides. This is given as patch so they are absorbed through the skin. If there was cells responsive to peptides you may have thought you could get a skin reaction apparently not and it looks like it works.  

The people in the trial had quite a high relapse rate,  compared to many more recent trials and am pleasantly surprised that the skin route is a good tolerogenic route but this is some nice evidence to support an autoimmune hypothesis.  

So maybe studies in mice are not that rubbish.

Bring on the next trial ASAP.

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MouseDoctor

11 comments

  • Transdermal induction of tolerance. Miller's group using modified WBCs to induce tolerance.This study only reinforces the importance of dysregulation in antigen recognition. Restoration of tolerance = holy grail…..beware non-believers.

  • That's funny. This is the same approach that Copaxone is based on (the very first MBP peptide drug). Yet everytime a new discovery is made about it we are subjected to the rumblings of MD2 about what a fraud it is and how he can't seem to grasp its mechanism of action. Im glad it is available to me now as well are many others who have benefited by it. Keep working on your pot based therapies, im sure it is doing you more good than those of us with ms.

    • Fair point but not quite the same a subcutaneous injection is not quite the same as transdermal batch and 1mg of defined peptide is not the same as 20mmg random mix. MSers can give T cell responses to the peptidesin the mix. This is not quite the case.

      I and MD2 do not buy the logic on which copaxone was originally based and the published pre-clinical data is very weak and probably selective. There are now a lot of published data that copaxone is doing stuff where myelin basic protein has nothing to do with the system. We can rationailse its action in other ways.

      In this study the effect on relapse rate was about 60% drop. This is twice 30%. Once glaterimer acetate, beta interferons and aubagio are at double their rate of success. MD2 will sing their praise too. At 30% we know you can do a lot better. Maybe with copaxone too….read Mike Boggild.

      Would I think the transdermal partch would work..well frankly no as it goes against immunological theory that has been consistent for many years. However it may be low dose tolerance and maybe if Th2/B cell responses are the problem rather than Th1. The data is more important than the theory.

      The MRI inhibition data of the patch is in a similar league to glaterimer acetate with is way down say compared to tysabri.

      That we are drip fed biology papers is probably a marketing ploy. It is correct that we point out the inconsistencies other you just get fed what marketeers what to feed you.

    • I guess the key point is that there is absolutely no evidence that the drug that is the quickest at sequestering, confining or deleting immune cells such that there is no MS activity in a two year study equates to long term efficacy.

      The name of the game is restoring self tolerance not immunosupression (at least in the inflamitory stage). GA appears to do just this and the long term studies are the most detailed. Yes they are not placebo controlled but it would be impossible (and inhumane) to have a 15 year long placebo controlled trial. But comparing the results to the natural history of MS, it is hard to deny its effect.

      I guess if a person has highly aggresive MS, Copaxone is not a good choice to shut down the BBB in comparison to drugs like Tsybari but I think most MS doctors would agree that Tsybari is not a long term solution. In my view the best solution may be a Tsybari-like drug to shut down activity quickly while at the same time using a MBP peptide drug to generate antibodies against the MBP peptides to induce tolerance. Once tolerance is re-established the patient should come off Tsybari.

  • The pot-based work is grounded on sound biology. However the days of the pot based theories are numbered…..neurologists mucking up clinical studies are seeing to that.

  • 10 placebo patients, 16 in the 1mg group, 4 in the 10mg group. A bit underpowered, don't you think?

    A quick look inside the full paper raises some questions:
    a. The mean EDSS score is 3.17 for the placebo group and 2.37 for the 1mg group
    b. Standard deviation of ARR is 1.1 for the placebo group and only 0.12 for the 1mg group. So there is great heterogeneity among the 10 placebo patients.
    c. The cumulative number of Gd+ lesions is compared between groups and the result of this comparison is named "reduction". Yet, there are no demographic data to inform us about the Gd+ lesions before and after treatment in EACH group.

    All in all, any more talking about this illusionistic study is a waste of time.

    • Terribly underpowered phase I and phase II always are therefore we need to wait for the phase III…..If your views are right it falls on a sword, if I am right it falls on a sword, but if it works then we are both wrong for different reasons and no one will give a stuff of what either you or I say…..which may not be far off the mark anyway.

      However I hope it did and does work.

    • As I said the ARRrate in the placebo group is high inother trials it is about 0.5 in the placebo group and 0.1-0.2 in the test group. The test group here was at 0.4-0.5 but placebo group wasmuch higher.

  • Data on the immunological response in this study were published in Ann Neurol 2010. I wonder whether their observations regarding the local and systemic immune regulatory response reconcile with the clinical response in the study.

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