Saturday, 21 February 2015

CrowdSpeak: Can a food supplement take on tecfidera?

Is it time to start online randomised trials of food supplements in MS? #MSBlog #MSResearch

"It looks as if these investigators have found a dimethyl fumarate (DMF, Tecfidera) me too. I sincerely hope they patented their data on ethyl pyruvate (EP) before publishing it. As we have said before without intellectual property (IP) on putative drugs the chances of getting them developed a treatment is almost zero. Patents are Pharma currency on which all business decisions are made; no patent no value. 

The findings in the study are interesting and take forward earlier observations that a large number of pro-inflammatory signaling pathways are redox sensitive. Redox sensitivity relies on the reduction potential of metabolic products and is a measure of the tendency of the chemical species to acquire electrons and thereby be reduced (a bit of deja vu from your chemistry classes). The fact that another metabolite does this opens up the field of anti-inflammatories to whole new class of agents. EP is a food supplement and hence can be purchased over the counter. I would not recommend you doing this as we have no idea what dose is required and what the longterm side effect profile is. Please not DMF causes lymphopaenia (low lymphocyte counts) and there has been a case of PML as a complication of this side effect.

It would be interesting if we could launch CrowdSourced online clinical trial of a food supplement to see if it has a disease-modifying effect in MS. This could be done in a similar way to how PatientsLikeMe tested lithium in motor neurone disease. What we would need are validated online outcome measures to assess the impact of a food supplement on MS and a central dispatching site to post active or placebo to all participants. Before embarking on this we would systems in place to deal with ethics, adverse event reporting and dealing with data validity. I am sure this all can be done in the MS space as well, but it needs a bit of thought."


Epub: Miljković et al. A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate. J Immunol. 2015 Feb 13. pii: 1402302. 

Background: Dimethyl fumarate (DMF), a new drug for MS treatment, acts against neuroinflammation via mechanisms that are triggered by adduct formation with thiol redox switches. Ethyl pyruvate (EP), an off-the-shelf agent, appears to be a redox analog of DMF, but its immunomodulatory properties have not been put into the context of MS therapy. 

Objective: We examined and compared the effects of EP and DMF on MS-relevant activity/functions of T cells, macrophages, microglia, and astrocytes. 

Methods and Results: EP efficiently suppressed the release of MS signature cytokines, IFN-γ and IL-17, from human PBMCs. Furthermore, the production of these cytokines was notably decreased in encephalitogenic T cells after in vivo application of EP to rats. Production of two other proinflammatory cytokines, IL-6 and TNF, and NO was suppressed by EP in macrophages and microglia. Reactive oxygen species production in macrophages, microglia activation, and the development of Ag-presenting phenotype in microglia and macrophages were constrained by EP. The release of IL-6 was reduced in astrocytes. Finally, EP inhibited the activation of transcription factor NF-κB in microglia and astrocytes. 

Conclusion: Most of these effects were also found for DMF, implying that EP and DMF share common targets and mechanisms of action. Importantly, EP had in vivo impact on experimental autoimmune encephalomyelitis, an animal model of MS. Treatment with EP resulted in delay and shortening of the first relapse, and lower clinical scores, whereas the second attack was annihilated. Further studies on the possibility to use EP as an MS therapeutic are warranted.

CoI: multiple

5 comments:

  1. Since DMF has no effect on brain atrophy it should be downgraded from "highly effective" to not effective. A DMF me too therapy seems to be a waste of time.

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    1. None of the DMTs, except maybe natalizumab, have any effect on brain atrophy. Reduction in lesion number is the benefit.

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    2. if you look at Prof H's slideshare slides you will see that natalizumab, alemtuzumab, fingolimod, laquinimod and BMT reduce brain atrophy.

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    3. Apologies, that should read Prof G and not Prof H.

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  2. Not a big fan of either BPA or this crowd funding initiative. In reality, and benefit will be 10 years away - look at Charcot project for how long things take (and this was a fairly straightforward trial). I wish the blog could focus on things in the shorter time frame - I need new therapies (neuroprotection / myelin repair in the next 3-5 years. The longer term initiatives will only benefit this diagnosed c.2025.

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