Wednesday, 11 February 2015

Getting rid of oligoclonal bands will Natalizumab inhibit progression

Bonnan M. Intrathecal IgG synthesis: a resistant and valuable target for future multiple sclerosis treatments. Mult Scler Int. 2015;2015:296184. doi: 10.1155/2015/296184

Intrathecal IgG synthesis is a key biological feature of multiple sclerosis (MS). When acquired early, it persists over time. A growing body of evidence suggests that intrathecal Ig-secreting cells may be pathogenic either by a direct action of toxic IgG or by locally secreting bystander toxic products. Intrathecal IgG synthesis depends on the presence of CNS lymphoid organs, which are strongly linked at anatomical level to cortical subpial lesions and at clinical level to the impairment slope in progressive MS. As a consequence, targeting CNS lymphoid lesions could be a valuable new target in MS, especially during the progressive phase. As intrathecal IgGs are end-products of these lymphoid lesions, intrathecal IgG synthesis may be considered as a specific marker of the persistence of these inflammatory lesions. Here we review the effect upon intrathecal IgG synthesis of all drugs ever used in MS. Except for steroids, all these therapeutic strategies, including rituximab, failed to decrease intrathecal IgG synthesis, with the exception of a questionable incomplete action of natalizumab. Thus, IgG synthesis is a robust marker of persistent intrathecal inflammation and its complete normalization should be one of the goals in future therapeutic strategies.


This is a review that states that essentially all treatments, except natalizumab, fail to control antibody production within the central nervous system. Is this the central problem for progressive MS,that the anti-inflammatories fail to get in the brain and so can't stop progression.

Therefore, natalizumab could stop progression if it were that simple.  Has this worked in the ASCEND trial of nataliziumab in secondary progressive MS. This should have finished in 2015. However, this study looks like it is being extended but now according to clinical trials.gov the completion date is 2017. Is this being extended because it is working?  Why would extend something that is not working?

Or will this address the thought of ProfG that there is a therapeutic lag? 

However the effectiveness at blocking depends on how you read the papers there may be others that affect OCB.

8 comments:

  1. As far as I am aware natalizumab does not stop conversion from RRMS to SPMS, just delays it. Isn't it so?

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    1. Re: "As far as I am aware natalizumab does not stop conversion from RRMS to SPMS, just delays it. Isn't it so?"

      Depends how you define SPMS. I think SPMS is there from the start. Yes, you are correct we some MSers developing progressive MS, but the majority of MSers who start early flat-line and do very well. Whether or not they will go onto to develop SPMS will only be answered in the future. The same thing happens with alemtuzumab.

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  2. I understand that we need more data. Natalizumab has been more widely used from around 2006? That is the patients with RRMS who were started on natalizumab early in the disease course have not had time to grow old enough to turn SP.
    I remember being offered natalizumab in 2006 at diagnosis (because of high lesion load). I read about it and as it was relatively soon after natalizumab was reintroduced to the market after being withdrawn because of PML risk, I chickened out and started interferon instead. I continued on interferon for some years and then stopped( flu-like symptoms, low mood, needle fatigue). I am still RRMS with the so-called "invisible symptoms". If I was started on natalizumab or alemtuzumab in 2006 everybody would be clapping for the effect of the medication. :-)
    MS takes time to develop into its full SP "glory".

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  3. Prof G,

    I'm sure as more highly effective anti-relapse drugs hit the market more and more MSers will flatline. I'm a classic case - two doses of Alemtuzumab has kept me NEDA (relapse / MRI / clinical examination) for the last 7 years. However, my EDSS remains 3 from the preAlemtuzumab relapses. Main issues relate to spinal cord damage - stiff knees and lack of sensation in feet, some spasticity in calves. Is anything on the horizon that might reduce these deficitis e.g repair treatment or better anti-spasticity drugs?

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    1. Good comment. I agree with you about the new drugs but and it's a big but we need neuroprotective agents to be administered at the same time to save as many nerve cells as posssible. if we can manage that I think we really will be getting somewhere.
      We have an anti-spastic drug in development that so far does not seem to have any of the negative side-effects of the existing medications.
      Hopefully it goes all the way to MSers.

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  4. Is it possible for a Neuro to make a diagnosis without ordering OCB test/analysis in lumbar puncture? My Neurologist claims that she didn't need to order OCB when I had my lumbar puncture last month. She also refuses to order an MRI with contrast.Claims the MRI without contrast from an ER visit 6 months prior, for Migraines (done by ER docs with no look for MS) didn't show any lesions/plaques & that an MRI with contrast is not indicated.

    I know this is a off the Natalizumab topic, but I'd really appreciate your opinion. Wondering if I should see a different Neurologist.Thanks

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    1. Enhancing lesions on an MRI are pretty much always there on the unenhanced scan, so if there are no lesions on the standard unenhanced scan there's pretty much no point in giving gadolinium. There are a few exceptions, for instance if you want to pick up enhancement of the nerves that arise directly from the brain (cranial nerves) or if you want to try to find enhancement of the lining of the brain, but usually there would be something different in the history or examination that would make you go looking for these things.

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  5. This is a little off topic but PLEASE HELP! My eight year old daughter has 2 CSF O bands and none in her serum. She also has some T2 white matter hyperintensities. I don't know if she has MS. Is there any way to get rid of her O bands? That is what I am researching and by this it isn't looking good. And do you all think this could be something other than MS?

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