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HERVs are officially a therapeutic target in MS

Discussion in 'Other Health News and Research' started by Ecoclimber, Sep 23, 2014.

  1. Ecoclimber

    Ecoclimber Senior Member

    Permission to repost courtesy of Prof. G.
    ECTRIMS 2014: HERVs are officially a therapeutic target in MS

    Can we reduce human endogenous retroviruses or HERVs with a treatment? #MSBlog #MSResearch
    "Just arrived back from Boston; exhausted physically, mentally and no doubt more to come with jet-lag.

    One of the highlights for me at ECTRIMS ( European Commitee for Research and Treatment in Multiple Sclerosis) was the interest in human endogenous retroviruses (HERV) and MS. The following is some interesting preliminary results from the clinical study of a monoclonal antibody targeting the envelope protein of a HERV associated with MS. What it shows is that this antibody decreases expression of this virus and the protein. Hopefully these effects will be associated with a reduction in MS disease-activity.
    This is what we are trying to achieve in our INSPIRE study using a drug, raltegravir, that targets HERV biology. We will also be doing biomarker studies to see if we down-regulate peripheral HERV expression.

    Please remember HERV transactivation, or expression in MS, may simply be an epiphenomenon, of inflammation. This is why it is so important to have to see if reduced expression of HERVs is associated with a therapeutic effect."


    GNbAC1 is an IgG4 humanized monoclonal antibody targeting and neutralizing pathogenic effects of MSRV-Env, a potent pro-inflammatory protein that also blocks oligodendrocyte precursor cell differentiation. This therapeutic target is an endogenous retroviral envelope from HERV-W family, which is abundantly expressed in microglia within active MS lesions and at the rim of chronic progressive plaques. HERV-W gag-encoded capsid protein is co-detected in MS lesions, which indicates HERV-W expression beyond the env-encoded pathogenic target.

    Follow-up mRNA expression in circulating blood cells of MS patients treated with GNbAC1 over the first six months of Phase IIa study with quantitative PCR targeting two different HERV-W genes, env and pol.

    Peripheral blood mononuclear cells (PBMC) of patients collected during the first 6 months of Phase IIa ( Identifier: NCT01639300) were assessed by real time quantitative polymerase chain reaction (RT-qPCR). Expression levels of messenger RNA (mRNA) were assessed by different primers/probe sets specific for retroviral env and pol HERV-W genes.

    At inclusion, no difference in HERV-W transcript levels was observed between patients being enrolled in both cohorts (2 and 6mg/kg) and between recruiting centres. Nonetheless, the different qPCR protocols showed the highest HERV-W mRNA levels in Primary Progressive MS (PPMS) patients. Despite low numbers, statistically significant correlations were found between HERV-W env and pol mRNA levels and disease duration and/or progression index.

    A decrease of all HERV-W mRNA levels was observed at the 6th GNbAC1 administration, when compared to basal values at inclusion in both cohorts. Statistical distribution of values measured before the first, third and sixth GNbAC1 injection in all patients showed unexpected decrease for both env and pol mRNA.

    Specifically binding to HERV-W envelope protein and neutralizing its pathogenic activity, GNbAC1 is not expected to impact HERV-W gene expression. A significant decrease of mRNAs encoding retroviral proteins from different HERV-W structural genes therefore appears unique for an anti-envelope antibody and evidences an effect on HERV-W expression itself.

    This study showed:
    i) a global anti-retroviral effect on HERV-W expression over six months of GNbAC1 treatment,
    ii) evidence, beyond MSRV-Env endogenous protein itself, of an association between HERV-W expression and MS and
    iii) PCR assays for potential companion diagnostic tests.

    Prior research article on HERV-W


    The DNA Copy Number of Human Endogenous Retrovirus-W (MSRV-Type) Is Increased in Multiple Sclerosis Patients and Is Influenced by Gender and Disease Severity
    Marta Garcia-Montojo mail, María Dominguez-Mozo, Ana Arias-Leal, Ángel Garcia-Martinez, Virginia De las Heras, Ignacio Casanova, Raphaël Faucard, Nadège Gehin, Alexandra Madeira, Rafael Arroyo, François Curtin, Roberto Alvarez-Lafuente, Hervé Perron
    Published: January 07, 2013 DOI: 10.1371/journal.pone.0053623


    Multiple Sclerosis is an autoimmune disease more prevalent in women than in men. Multiple Sclerosis Associated Retrovirus element (MSRV) is a member of type-W endogenous retrovirus family (HERV-W), known to be associated to MS. Most HERVs are unable to replicate but MSRV expression associated with reverse-transcriptase activity in MS would explain reported DNA copy number increase in MS patients. A potential link between HERV-W copies on chromosome X and gender differential prevalence has been suggested. The present study addresses MSRV-type DNA load in relation with the gender differences and clinical status in MS and healthy controls.


    178 MS patients (62.9% women) and 124 controls (56.5% women) were included. MSRV env load (copies/pg of DNA) was analyzed by real time qPCR with specific primers and probe for its env gene, in DNA from peripheral blood mononuclear cells (PBMCs). MSRV load was more elevated in MS patients than in controls (p = 4.15e-7). MS women presented higher MSRV load than control women (p = 0.009) and MS men also had higher load than control men (p = 2.77e-6). Besides, women had higher levels than men, both among patients (p = 0.007) and controls (p = 1.24e-6). Concordantly, EDSS and MSSS scores were higher among female patients with an elevated MSRV load (p = 0.03 and p = 0.04, respectively).

    MSRV increases its copy number in PBMC of MS patients and particularly in women with high clinical scores. This may explain causes underlying the higher prevalence of MS in women. The association with the clinical severity calls for further investigations on MSRV load in PBMCs as a biomarker for MS
    Last edited: Sep 24, 2014
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