Homework: progressive MS is?…..Discuss

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What drives progressive MS and what is the solution? You get the views of ProfG but this is just one opinion and there are others. If you like lab Lessons have a read of this review it gives a different take on what is going on and what the solutions may be

It is an opinion and not necessarility the right opinion and not necessarilly the same opinion as me but it is someone elses opinion.

What do you think. They say

Correale J, Gaitán MI, Ysrraelit MC, Fiol MP. Progressive multiple sclerosis: from pathogenic mechanisms to treatment. Brain. 2017 Mar 1;140(3):527-546. doi: 10.1093/brain/aww258.

One suggestion that brain damage is driven by inflammatory processes similar to those observed during RRMS; but that during progressive disease stages, a microenvironment is created within the CNS favouring homing and retention of inflammatory cells, ultimately causing disease-modifying therapies to become largely ineffective (Frischer et al., 2009).

Secondly, multiple sclerosis starts out as an inflammatory disease, but after several years, a neurodegenerative process independent of inflammatory responses becomes the key mechanism responsible for
disease progression (Meuth et al., 2008).

Finally, multiple sclerosis could primarily be a neurodegenerative disease,
with inflammation occurring as a secondary response, amplifying progressive states (Barnett and Prineas, 2004; Kassmann et al., 2007). Clearly these different mechanisms are not mutually exclusive and could act together.

If the answer is EAE…What is the question?

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MouseDoctor

8 comments

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  • Guessing the efficacy of BTKi’s on PMS will answer how accurate opinion 1 is.

    Opinion 2 sounds nuts,

    Opinion 3 lacks evidence?

  • So MS is a disease that is degenerative independently of the immune system whose response is just secondary? It’s like that first you have degeneration of joints in rheumatoid arthritis or of organs in SLE and then you have immune system attacks. Not so convincing to me.
    Considering that therapies and treatments that hit heavily the immune system can lead to long term remission in some patients with those diseases I would ask: where is the degeneration that triggers immune system to attack in those people? Why does it stop?
    If immune response is secondary why it does not recur after blowing up the immune system?

  • If the answer were EAE we would’ve had the solution a long time ago. Seems that, long run, EAE only provides more questions. MS scientists studying EAE = dogs barking up wrong tree.

    You once stated the percentage of successful EAE treatments that translated over to humans, and it was some infinitesimal number. Would you mind stating that again? I believe it was well under .1%.

  • Progressive MS is ………

    Something that effects all sub groups of MS such as grey matter atrophy early in the disease

    It needs tons more research on how to significantly slow or completely stop it.

    A lot of focus on white matter lesions but not so much on whole brain atrophy for example which ultimately leads to more significant disability.

    Hopefully BTKi treatments, remyelination treatments and maybe a mitochondrial treatments will help with this, but there no guarantee. Positive lifestyle choices will make a difference in the short, medium and long term on how MS progresses.

    But as we’re are not fully there yet, we have to wait for the great research being done to shine some light and get some answers and keep pushing forward.

  • I was diagnosed around the same time as the Barnett and Prineas paper (2004) which I remember caused a big stir among the MS research community. Nothing really came of it. Another storm in a teacup for MS researchers.

    The honest assessment of what Progressive MS is / what drives it, is that the MS researchers haven’t got a clue. Let’s be truthful – opinions relating to what Progressive MS is, are like a**eholes – everybody has one (or at least every MS researcher). MS is no different from MND or the dementias (or a bucketful of other CNS degenerative diseases) – there are no experts / no definitive understanding of the disease processes. What happened to Prof G’s 15 year experiment (using Alemtuzumab results) to test whether MS is autoimmune (probably caused by a virus) or neuro-degenerative? We should have an answer by no.

    Surely the answer must lie with the patients at the earliest stage of the disease process eg paediatric cases. Testing drugs or undertaking MRIs on patients who’ve had the disease for 20 years won’t yield results – too much damage has taken place.

    Another paper, produced by another research group in another country:

    https://multiplesclerosisnewstoday.com/news-posts/2021/01/19/brain-changes-in-relapsing-ms-found-to-follow-pattern-in-tracking-study/

    All MS patients want is treatments that stop progression / accruing disability. Unfortunately, we seem to be no nearer to this Holy Grail. The recent failures of the MS-SMART trials and three remyelination trials (in 2020) really highlight the lack of progress in understanding what Progressive MS is and how to treat it.

    I did take a bit of hope from the International Progressive MS Alliance formed in 2014 with the goal “to address the urgency to find solutions for everyone living with progressive MS, irrespective of location. We must work together to uncover the answers and bring forth solutions.” I was pleased to see that one of the key scientists running the Alliance was awarded a prestigious MS prize and c. £100,000:

    https://multiplesclerosisnewstoday.com/news-posts/2021/01/04/professor-alan-thompson-leader-in-research-on-progressive-ms-wins-sobel-prize/

    However, even the Alliance can’t provide an answer as to what Progressive MS is!

    • The 2020 Sobek Research Prize has been given to Alan J. Thompson, MD, a physician scientist with University College London, for his pioneering work in progressive multiple sclerosis (MS), the National MS Society announced.

      At this point, seeing that, I am reminded that Tom Lehrer memorably pointed out about Henry Kissinger winning the Nobel Pwace Prize, that “satire is dead”.

  • I had it all figured out but my dog ate my homework 🙁

    From what I remember B cells in meningeal lymphoid tissue are key to smouldering MS and neurodegeneration…….bad dog.

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