Monday, 29 July 2013

Tysabri and Endogenous Retro virus.

Arru G, Leoni S, Pugliatti M, Mei A, Serra C, Delogu LG, Manetti R, Dolei A, Sotgiu S, Mameli G.Natalizumab inhibits the expression of human endogenous retroviruses of the W family in multiple sclerosis patients: a longitudinal cohort study. Mult Scler. 2013 Jul 22. [Epub ahead of print]

BACKGROUND: Several viruses were reported as co-factors triggering the pathogenesis of multiple sclerosis (MS), including the endogenous retroviruses of the HERV-W family, that were also proposed as biomarkers of disease progression and therapy outcome.

OBJECTIVE:The objective of this article is to clarify whether in MS patients treatment with natalizumab has effects on MSRV/syncytin-1/HERV-W expression and the possible relationship with disease outcome.
METHODS:Peripheral blood mononuclear cells were collected from 22 patients with relapsing-remitting disease, at entry and after three, six and 12 months of treatment with natalizumab. The cell subpopulations and the expression of MSRVenv/syncytin-1/HERV-Wenv were analyzed by flow cytometry and by discriminatory env-specific RT-PCR assays.


RESULTS: By flow cytometry the relative amounts of T, NK and monocyte subpopulations were shown to remain fairly constant. A relative increase of B lymphocytes was observed at three to six months (p = 0.033). The MSRVenv and syncitin-1 transcripts were reduced at six to 12 months of therapy (p = 0.0001). Accordingly, at month 12, the plasma-membrane levels of the HERV-Wenv protein were reduced (p = 0.0001). B cells, NK and monocytes but not T cells expressed the HERV-Wenv protein. None of the patients relapsed during therapy.
CONCLUSION: Effective therapy with natalizumab downregulates MSRV/syncytin-1/HERV-W expression.


The ProfGs think that viruses are a central problem in MS and have put their necks on the block and started the Charcot Project..recruiting now. 

Human endogenous retrovirus or HERV have been implicated. 

They are present in your DNA, in every cell, and can become reactivated to make viral particles. In this study people getting tysabri made less HERV and had no relapses. Is this the reason why tysabri works?..

I doubt it...it works because it stops white cells getting in the brain. 

However, maybe it is inflammation that triggers HERV expression, get rid of inflammation and the HERV go. Therefore could HERV expression by the consequence rather than the cause of MS. If so is the Charcot Project treating the chicken and not the egg.

CoI: None

7 comments:

  1. That is a real bummer, people were really hoping that charcoot will be breakthrough.

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    Replies
    1. It's all supposition at this stage. Once the Charcot Project is completed we may have a clearer idea about the role of HREVs and MS. No reason to get despondent yet!

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  2. Prof Gold

    The INSPIRE Clinical trial will provide us with important information regarding HERVs and RRMS. I think we should be a little patient and see what we find. I can understand that a quick resolution is what everybody wants. I suggest we should be far from despondent.

    ReplyDelete
    Replies
    1. Nice to hear from you Prof Gold. Please post and comment more often

      Delete
  3. HERV-K family and HIV-1 levels and subsequent drop in CD4+ levels is also being studied http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0041021
    Is it incorrect to use the analogy of HIV =natalizumab causing reduction in CD4+(by different means)? In either case decrease in CD4+ is associated with decrease HERV-K or HERV-W. There seems to be mechanistic similarities.

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  4. No need to get dispondent yet.
    Mechanism for charcot May have nothing to do with lymphocytic herv. Stuff in cns May be more important.

    When cells divide retro virises are easier to spot.

    Take most mouse cell lines they are fizzing with viruses. I made a B cell line once and did electron microscopy and is was shedding virus like mad. I then looked at standardcell lines and the same.

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  5. So if tysabri affects lymphocyte activation herv can go down.

    ReplyDelete

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