Sunday, 30 June 2013

Gilenya affecting the processes driving progression?

Alzheimer's disease (AD) as a neurodegenerative brain disorder is the most common cause of dementia. To date, there is no causative treatment for AD and there are few preventive treatments either. The sphingosine-1-phosphate receptor modulator FTY720 (fingolimod) prevents lymphocytes from contributing to an autoimmune reaction and has been approved for multiple sclerosis treatment. In concert with other studies showing the anti-inflammatory and protective effect of FTY720 in some neurodegenerative disorders like ischemia, we have recently shown that FTY720 chronic administration prevents from impairment of spatial learning and memory in AD rats. Here FTY720 was examined on AD rats in comparison to the only clinically approved NMDA receptor antagonist, Memantine. Passive avoidance task showed significant memory restoration in AD animals received FTY720 comparable to Memantine. Upon gene profiling by QuantiGeneplex, this behavioral outcomes was concurrent with considerable alterations in some genes transcripts like that of Mitogen Activated Protein Kinases (MAPKs) and some inflammatory markers that may particularly account for the detected decline in hippocampal neural damage or memory impairment associated with AD. From a therapeutic standpoint, our findings conclude that FTY720 may suggest new opportunities for AD management probably based on several modulatory effects on genes involved in cell death or survival.

Whilst this may seem inherently uninteresting to MSers as this is about studies in animals related to Alzheimer's disease, the interesting thing is that it appears to be influencing a degenerative condition which is not typically associated with autoimmunity. So does this mean that fingolimod and or siponimod may be useful for progressive MS. The studies are ongoing.


  1. MouseDoc, you have gone on record criticising the basic science supporting theories that fingolimod may be useful in combating progressive MS.

    1. Yes I have been critical....not because it is impossible but because we should not let the spin doctors give the impression that is does something when the data do not support such conclusions. This creates false impressions.

      Our own data may question whether benefit will occur independent of affect on peripheral inflammation. However we now must wait and see. The PPMS trialis fully recruited and now it is a question of waiting for the data.

      If I am wrong I will be happy and eat humble pie, I hope I am wrong.

      I doubt in this case that fingolimod is working by blocking immune cells in the lympg glands. This is why I broght it to your attention as theremay be people considering the siponimod study

  2. But MS isn't really an autoimmunity disease, I thought, or at least was led to believe. I have read that MS basically is a neuro-degenerative illness that provokes an autoimmunity response. I'm sure I read such things on this blog.

    1. You may have read them in the comments from an MSer or a post such as by Peter stys. They are not my words but I will sit on the fence and say there is still reason to believe that an immune response is a cause and not a consequence.

      In animals it is clear that autoimmunity can create the neurodegeneration

      MS is an immune-mediated disease...treatment effects tell us that.

      Is there an autoimmune component....I would say yes. Is MS autoimmune? I would say unproven. In MS primarily a neurodegenerative condition I would say likewise unproven,

      I do not buy the protective autoimmunity theory if this were the case then the balanceofremoval ofimmune response would be a negative is not. Does the immune response promote repair, yes sure this is what inflammation is all about.

      Prof G thinks a virus is at the centre of the problem


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