Monday, 26 November 2012

Research: blocking relapses inhibits nerve damage

Gunnarsson et al. Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab. Ann Neurol. 2011;69:83-9

OBJECTIVE: The impact of present disease-modifying treatments (DMTs) in multiple sclerosis (MS) on nerve injury and reactive astrogliosis is still unclear. Therefore, we studied the effect of natalizumab treatment on the release of 2 brain-specific tissue damage markers into cerebrospinal fluid (CSF) in MS patients.

METHODS: CSF samples from 92 patients with relapsing forms of MS were collected in a prospective manner prior to natalizumab treatment and after 6 or 12 months. In 86 cases, natalizumab was used as second-line DMT due to breakthrough of disease activity. The levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) were determined using highly sensitive in-house developed enzyme-linked immunosorbent assays.

RESULTS: Natalizumab treatment led to a 3-fold reduction of NFL levels, from a mean value of 1,300 (standard deviation [SD], 2,200) to 400 (SD, 270) ng/l (p < 0.001). The later value was not significantly different from that found in healthy control subjects (350 ng/l; SD, 170; n = 28). Subgroup analysis revealed a consistent effect on NFL release, regardless of previous DMT or whether patients had relapses or were in remission within 3 months prior to natalizumab treatment. No differences between pre- and post-treatment levels of GFAP were detected.

INTERPRETATION: Our data demonstrate that natalizumab treatment reduces the accumulation of nerve injury in relapsing forms of MS. It is anticipated that highly effective anti-inflammatory treatment can reduce axonal loss, thereby preventing development of permanent neurological disability.



Reducing the immune attack with tysabri, blocks the accumulation of a damaging immune response within the CNS, so nerves do not get damaged and break down Therefore less neurofilament light, a structural molecule of nerves, gets in the CSF. So before treatment there is the amount in the red box after treatment we are in the green which is within normal levels (far right).Therefore blocking relapses is clearly a good thing.

10 comments:

  1. Do you think the mechanism of how relapses are blocked may play a role?

    So something else could also block relapses without making a difference to nerve damage

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    1. Most effective relapse blockers stop white blood cells arriving in the brain, so they do not get there to cause damage so I would suspect the same. However that is until I am proven wrong and may be tysabri is affecting a cell subtype that others may not.

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    2. Does anybody know about neurofilament levels of MSers who have no lesions or relapses on one of the CRAB DMTs?

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  2. It has also been published recently, that patients with SPMS treated with Tysabri also have their CSF neurfilament light levels (NFL) reduced, justifying the ASCEND trial on-going for SPMSers treated with Tysabri. Is then your inference that relapses do matter for disease progression not really linked to relapses but to other mechanism of progression? (neurodegeneration)

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  3. I was looking for this at ECTRIMS web site yesterday as I have not seen this but Prof G told me about it. But the web site was not working properly. Who was the first authors name?. If it was present above the normal level it could be telling us that there may be some other mechanism a foot still causing progression so the question is will ASCEND show a change in slope, I do not expect it stopping progression (my personal opinion only). However I would not be surprised if it went down because I still think there will be some element of inflammation ongoing in progressive MSers. This can be found out in subset analysis to see if those benefiting are still relapsing.

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    Replies
    1. Christensen et al. (Copenhagen)... http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=158391&XNSPRACHE_ID=2&XNKONGRESS_ID=171&XNMASKEN_ID=900

      No Relapses in the 12+12 SPMS+PPMS and biomarkers (including neurofilaments levels in CSF) statistically significantly improved over 60 weeks

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    2. Thanks but they have not got their presentation on ECTRIMS, so will have to wait until it is published. The inference is that progression is being inhibited.

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  4. This study proves that the immune response creates more NFL than normal. It does not prove that the NFL come from healthy, undamaged axons. If the axon is already damaged, then the immune cells that Tysabri blocks are necessary for the its disintegration. Tysabri reduces the rate of disintegration by preventing immune cells clearing the debris and leaving this job to microglia. That's why the NFL levels are near to normal but slightly elevated.

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    Replies
    1. How are you so certain?
      Shouldn't you say 'another explanation could be that ...'

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    2. Re VV
      Why break a habit of a lifetime:-)

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