Monday, 17 June 2013

Tysabri treatment blocks nerve loss and atrophy.

#MSResearch #MSblog Proof that relapses are not good for you so we need to stop them.


BACKGROUND: Neurofilaments are promising biomarkers in multiple sclerosis (MS) and increased levels in cerebrospinal fluid (CSF) indicate axonal damage or degeneration. In a previous study, neurofilament light chain (NfL) levels in CSF of relapsing remitting (RR) patients with MS were normalized by natalizumab treatment.


AIMS OF THE STUDY: We compared the coherence between NfL and neurofilament heavy chain (NfHSMI 35 ) levels in longitudinal CSF samples in a subset of these patients.

METHODS: In 30 patients with RRMS, CSF was obtained prior to and following 12 months of natalizumab treatment. 


RESULTS: NfHSMI 35 decreased in 73.3% and NfL in 90% of the MSers following natalizumab treatment (32.4 vs 27.4 pg/ml, P = 0.002 and 820 vs 375 pg/ml, P < 0.0001). MSers experiencing a relapse showed higher NfHSMI 35 levels compared with MSers in remission (47.7 vs 27.6 pg/ml, n = 8, P = 0.001). This difference was less obvious for NfL (1055 vs 725 pg/ml, P = 0.256). In patients in remission, NfL levels were lower following natalizumab treatment (830 vs 365 pg/ml, n = 20, P = 0.0002), whereas the same comparison failed significance for NfHSMI 35 (28.3 vs 26.9 pg/ml, P = 0.086).
 
CONCLUSIONS: We confirm previous findings, indicating reduced axonal damage under natalizumab treatment by measuring NfHSMI 35 , using an assay with independent methodology. In comparison with NfHSMI 35 , NfL changes were more pronounced and the treatment effect also included patients in remission. Our results suggest that NfL is superior over NfHSMI 35 as therapeutic biomarker and is a promising candidate to measure neuroaxonal damage in MS treatment trials.



Neurofilament are not just promising biomarkers, they ARE biomarkers. I can't wait for the lamotrigine trial data to come out....It didn't work I hear you say....there is more in the story to come, but that's for another day.

As we and Prof G have been saying for sometime now, inflammatory responses in your brains are not a good thing. 


Treating early and aggressively with highly active DMT will be beneficial. This is yet further clear evidence for this concept and only an ostrich should not be able to see this. On balance allowing an immune response into the brain, which is what Tysabri stops, is not beneficial. Having relapses are damaging just as was told from EAE studies.

When nerves are damaged they release their content and this can be measured by looking for nerve structural proteins (Neurofilaments) in the brain fluid and sometimes in the blood. High levels in brain fluid imply that there is brain damage going on. This study repeats earlier studies published in Aanals of Neurology that clearly show that Tysabri treatment slows nerve loss. Therefore the blocking lesion formation and relapse is clearly a good thing and to deny this is simply ignoring the data. 

There are different forms of neurofilament (SMI35 is the name of the antibody which detects heavy chain, SMI32 detects a phosphorylation variant which is found in unhealth nerves) which are structural proteins. The smaller one (Neurofilament Light) is better as a predictory of nerve damage. We know this already, but yet more evidence that use of measuring neurofilament levels in trials is a good thing.

So when some of you, in denial, say DMT are a waste of time...think again! We need to get people on highly active DMT and "Say no to brain shred".

CoI: Team G were involved in this study.

14 comments:

  1. OK. I say No to Brain Shred.

    On another tack, was idley wondering whether any MSers have spoken about a class action against all the neurologists who didnt prescribe DMTs through 90's and after? Usually improves contemporary behaviour if nothing else...

    ReplyDelete
  2. Neuologists were prescribing the tools available.
    Suing it is the lawyers whogain. Get government to let second line therapies be first line give mser the choice

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  3. You only need to have moved around the country to know there was no consistency and some where much more up to speed than others so far as knowing about the tools.

    What do you mean by second line be first line? P :)

    ReplyDelete
    Replies
    1. In UK first line is beta interferons and glaterimer acetate
      you only get access to second line (Gilenya and Tysabri) after you fail the first line (or if you have very active disease you may get say tysabri first line. Therefore it could be years before you get the highly active DMTand the risks that come with their use.

      In other countries this is not necessarily the situation.

      Delete
  4. This post is nonsense! If Tysabri is so effective at curtailing axonal damage the it will have worked in progressive forms of MS, which it does not. This is all selective and manipulative reporting that exists to promote the sale of pharmaceuticals. There is a daily propaganda to publicise the use of DMTs and never once does this blog report on the need to live a healthy and clean lifestyle to avoid damage by MS. It's always drugs, drugs, drugs!

    This blog avoids holistic approaches. It only believes in niche medicines that cost a fortune and barely work in most cases.

    ReplyDelete
    Replies
    1. Why is this post nonsense?
      The point is that Tysabri reduces axonal damage and thus in the longer term should slow the rate of progression. It won't work in progressive MS because the damage has already occurred and so is too late for Tysabri's mode of action, which is why we need neuroprotectants for this phase of the disease.
      This blog is certainly not propaganda, merely reporting on the research/clinical findings as the become available.
      Everyone here would support a healthy lifestyle but the evidence that this will have a great effect on your disease ain't great.
      If there were good clinical studies supporting this they would be reported here.
      The take home message is that (the new) drugs do work and to pretend otherwise is dishonest.

      Delete
    2. and it's not exclusive, I'm on Tysabri but that doesn't cut me off from taking vD or eating, living in a way that I find to be the best for me...
      So please stop patronizing me like I cannot make my own decisions just because I'm using a DMT. It's not like I'm being taken hostage by Big Bad Pharma..
      //Swedish Sara
      Best regards
      /Swedish Sars

      Delete
    3. Dear Anon 11:56

      Nonsense....we do do holistic posts but they do not appear in the literature very often.

      Plus there are usually reports of such low quality that the resiults are not worth posting. However do the searches and you can find some.

      It is about class 1 evidence and not something we read is the newspaper

      Delete
  5. My personal observations are that those that start tysabri earlier do better. Those that its used as a last resort still battle the disease every day

    ReplyDelete
    Replies
    1. I predict that tysabri will not slow progressive MS.
      Will it slow the rate of progression that is the question.

      Delete
    2. By reducing axonal damage as measured by neurofilament subunits does this suggest efficacy in progressive disease? Effector CD8 T-cells have been implicated in SPMS and progressive disease. Maybe the direct attack by these cells can be lessened by blocking expressed integrins.

      Delete
  6. Every thing has been implicated but theproof islacking. Less neurofilament is less nerve damage isless progression. However how do CD8 cellswork. They are stimulated in context of MHC class I, I think nerves are not expressing this.

    ReplyDelete
    Replies
    1. Quite right MD, there is no constitutive expression of MHC class I but can be upregulated in certain conditions.
      http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001354

      Delete
    2. Interesting that epigenetic factors may be involved with chronic conditions e.g. MeCP2).

      Delete

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