Friday, 16 October 2015

Fampridine as an immunomodulator

You asked is fampridine a DMT and MD2 thought why would a symptom control drug work as a DMT.

Some potassim channels are on immune cells and so blocking them may be of value and there is a literature on potassium channels

Treatment of multiple sclerosis with a combination of laquinimod and fampridine patent WO2013US50001 20130711.

4-amino pyridine is the active part of fampridine which is a slow release formualtion of 4-AP.
Are the  lines with the crosses (4-AP) really different from the small circle? So if we listen to the ARRIVE guidelines for EAE you should ask...Where is the evidence of variation i.e. the standard deviations because without them you cannot tell how good the data is and without knowing how many animals got sick and to what severity they got the lines are relativiely meaning less.

Baker D, Amor S. Publication guidelines for refereeing and reporting on animal use in experimental autoimmune encephalomyelitis.J Neuroimmunol. 2012 Jan 18;242(1-2):78-83.

The "smack you in the eye test" looks like the peak of vehicle verses 4-AP (2.5mg/kg is no difference) probably true at 5mg/kg and is the really any difference between Laquinimod alone and laquinimod + fampridine. The sack you in the eye test say no to me what does it say to you? However the patent is all about the added value of mixing the two compounds.  This is patent is not peer reviewed properly and one should asked about the value of mixing a DMT with low efficacy with a symptom control drug in an assay aided at showing a DMT-like effect.

Is there a "building-site" effect.......The animals feel like crap and so are stressed-out (as occurs due to construction work  nearby) and so the steroid response inhibits EAE or is it a real immunomodulator effect.

Others think not and say 4-AP has no effect on EAE
Göbel K, Wedell JH, Herrmann AM, Wachsmuth L, Pankratz S, Bittner S, Budde T, Kleinschnitz C, Faber C, Wiendl H, Meuth SG. 4-Aminopyridine ameliorates mobility but not disease course in an animal model of multiple sclerosis. Exp Neurol. 2013; 248:62-71.

Uitdehaag BM, Polman CH, de Groot CJ, Dijkstra CD. Effect of K+ channel blockers on the clinical course and histological features of experimental allergic encephalomyelitis.Acta Neurol Scand. 1994; 90:299-301.

others say

The effect of fapridine on the course of MS is something that we would like to know.


  1. This is also a question I have, I remember that I asked on the blog in jma last posting on the Blockers Potassium ... I know three people who used to fampridine. Two have MSRR and the other has MSPP. Of those who have MSRR one is in Natalizumab and the other is in Fingolimod, they had improvements in walking, nothing else. But what has MSPP had a significant improvement even in the absurd fatigue he felt, just did not ask whether this effect has been sustained for longer ...

  2. The above supports the view I formed some time ago that animal models and EAE are next to useless as a research tool for MS. We now have 12+ treatments for RRMS and a couple in the pipeline for PPMS. There are human trials looking at remyelination therapies and stem cell therapies... There are human trials looking at anti-virals and neuro-protection. Why do we need experiments on mice apart from giving PHD students a their research project? Prof B is a nice man, but will persist with EAE long after MS has been cured. It's over Prof B - you need to move on. Take the dead parrot sketch from Monthy Python and insert EAE for the Parrot. You are the Michael Palin shopkeeper - you cannot accept that EAE is deceased.

    1. Well, like, that's just your opinion, man. Where do you think the ideas come from for remyelination/stem cell therapies? The human neuroprotection trials are a direct result of OUR work in EAE, Fact and there's more to come. Plus cannabis for spasticity is as a direct result of our EAE work and of course our new drug that is now in clinical trial for spasticity.
      Not a bad track record for a next to useless model.

    2. But when will I be in a position to go to my GP or Pharmacist and ask for some neuroprotection tablets, a remyelination injection, an anti-spasticity pill? Researchers brag on about what animal models have achieved, but it's made no difference to my life. It's always jam tomorrow, lots more in the pipeline... I'll eat my hat when I see outcomes that benefit MSers.

    3. Which sauce will you be having with your hat?

    4. I like horseradish. And I will be joined by the two Mouse doctors at a nice French restaurant in Belgravia. Your meals and the barrel of ale which MD1 will consume will be my treat. You will see that Mr Angry of Tunbridge Wells can be quite nice.

    5. Lovely, I look forward to it. What stye of hat? I envisage a jaunty trilby.

    6. But when will I be in a are moaning at the wrong people...we have no control on how quickly and if treatments get developed on not take a deep breathe and vent your anger elsewhere, scientists create the ideas, clinicians try to implement them is in the hands of the regulators and notably the accountants. They decide if they can make enough money out of you and if they think they can they may develop something if they can't they don't and let things sit on the self.

      When I see outcomes that benefit MSers....start chomping mate because those drugs being used by some MSers all have animal work at their core.

      As to neuroprotection and repair...there are a number of trials onggoing and recruiting why not volunteer if you are eligiible

    7. Why do we need mouse experiments so pharma can file patients see above and then they have the confidence to invest $100,000,000 to do the studies needed to deliver drugs to you

  3. It is immensely frustrating as a patient to know that the animal models being used to research your disease:

    (a) do not recapitulate human pathology as closely as science would hope
    (b) cause severe suffering to the poor animals involved
    (c) appear to result in very little clinical benefit in comparison to the resources invested
    (d) seem to be used & reported in badly designed experiments

    It‘s easy to lash out at those actually doing the work, but this only tends to produce an equally negative reaction from the researchers themselves, and will eventually result in channels of communication closing down, which doesn't help anybody!

    Personally, I loathe the continued use of the EAE mouse as a model of my own condition, but I am also painfully aware that it has helped produce the treatments currently available to me, and - at the moment - there is no viable alternative. The models can, however, be refined to limit the extent of animal suffering.

    We need to see far more effort and resource put in to developing non-animal alternatives that reflect what we see in real, human MS (and many other conditions besides). The research councils and medical charities both need to take this on board and push for the development of replacements. It won’t be straightforward by any means - it isn’t for most disorders - and neurodegenerative and autoimmune disease are particularly problematic, but it will be infinitely more unlikely if we don’t start trying!

  4. Dear Dr Doox
    Are you taking to us directly or to EAEers and scientists in general

    There is no point taking you to task for (a-d) I could defend our position against each of your claims. However I am not going to defend all of my fellow EAEers. I hope you are aware that we too have issues with our peers and go on the record to point these things out.

    Maybe you should check out

    The National Centre for the Refinement reduction replacement of animals in research (

    The 3Rs are central to approvals to do animal work in the UK and it is also there for the EU too.

    The refined EAE model of EA took five years to get funded to do and I still have not got any funding to use human brains for research. It has already delivered a drug that works in humans. I have spent years trying to fund work that involves no animals but you need preliminary data and it costs to do that work.

    Fund this and no animals will be used but it needs resource to develop it.

  5. Thanks MD.

    I appreciate the response. I was talking to a mixture of audiences, really, and simply externalising some frustrations that many of us MSers have, whilst trying not to be too 'binary' or provocative!

    Yes, I'm aware of the work that NC3Rs do, and yes, I have read Katie's PLoS one paper - it was her paper to which I was referring in my comment about refinement.

    Is the ON model used routinely now (or even across the board?), or is it just reserved for ON-specific studies?

    1. Not peers are rather blinkered and perform their experiments in a prescriptive formulaic way. This means so much of what is produced may turn out to be of limited value from a translation neuroscience perspective.

  6. What are the labels on the axis? (always label axis ;). Fampridine seems more effective than laquinimod as DMT. Why not a human trial using Fampridine as DMT (it might please both animal activist and the others)?


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