Saturday, 31 March 2012

Research: Endogenous retrovirus and MS


Background: The envelope protein from multiple sclerosis (MS) associated retroviral element (MSRV), a member of the Human Endogenous Retroviral family 'W' (HERV-W), induces dysimmunity and inflammation.

Objective: The objective of this study was to confirm and specify the association between HERV-W/MSRV envelope (Env) expression and MS.

Methods: 103 MS, 199 healthy controls (HC) and controls with other neurological diseases (28), chronic infections (30) or autoimmunity (30) were analysed with an immunoassay detecting Env in serum. Env RNA or DNA copy numbers in peripheral blood mononuclear cells (PBMC) were determined by a quantitative polymerase chain reaction (PCR). Env was detected by immunohistology in the brains of patients with MS with three specific monoclonals.

Results: Env antigen was detected in a serum of 73% of patients with MS with similar prevalence in all clinical forms, and not in chronic infection, systemic lupus, most other neurological diseases and healthy donors (p<0.01). Cases with chronic inflammatory demyelinating polyneuropathy (5/8) and rare HC (4/103) were positive. RNA expression in PBMC and DNA copy numbers were significantly elevated in patients with MS versus HC (p<0.001). In patients with MS, DNA copy numbers were significantly increased in chronic progressive MS (secondary progressive MS vs relapsing-remitting MS (RRMS) p<0.001; primary progressive MS vs RRMS -<0.02). Env protein was evidenced in macrophages within MS brain lesions with particular concentrations around vascular elements.

Conclusion: The association between MS disease and the MSRV-type HERV-W element now appears quite strong, as evidenced ex-vivo from serum and PBMC with post-mortem confirmation in brain lesions. Chronic progressive MS, RRMS and clinically isolated syndrome show different ELISA (Enzyme-Linked Immunosorbent Assay) and/or PCR profiles suggestive of an increase with disease evolution, and amplicon sequencing confirms the association with particular HERV-W elements.

                                                            HERV in an astrocyte


Thus there is now a bit more evidence to suggest that the Prof Gs may have something with HERV W the Charcot Project, (a plan to target EBV and HERV in MS) so now all they have to do is get that trial to deal with HERVs off the ground. It is interesting that other studies with a different HERV-FC found higher levels in RRMS than progressive MS.

8 comments:

  1. Do anti retrovirals work against all types Of HERV? If HERV-W is elevated in prog.MS, could anti-retrovirals decimate it and lead to a halt in progression, or is it too late once you are on the neurodegenerative pathway?

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  2. Re: "Do anti retrovirals work against all types Of HERV? If HERV-W is elevated in prog.MS, could anti-retrovirals decimate it and lead to a halt in progression, or is it too late once you are on the neurodegenerative pathway?"

    No; not all anti-HIV drugs work against HERVs. Some will, which is why we are trying so hard to get funding for an anti-retroviral trial. It is a trial that needs to be done; urgently!!

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  3. There's a fascinating article on potential directions for antiviral drugs on Wired: http://www.wired.com/wiredscience/2012/03/ff_antivirals/all/1

    I would like to know if you think that antivirals will be effective in progressive MS or will that be too late?

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  4. We need to get the studies off the ground giving them their best chance of working, then if they do not it is back to the drawing board

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  5. There is no reason at the moment to think that if anti virals are active that there is not benefit to be had late as well as early. There are just more issues to deal with when treatment is started late on, so as with everything the earlier you start the better and in some cases this would be beofre diagnosis

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  6. Thank you for the article Unknown.
    It says "Even when we’re perfectly healthy, we have trillions of viruses inside of us. Scientists are only beginning to survey this viral ecology, but some suspect that it may actually be essential to our health."
    I think a broad spectrum antiviral could be dangerous.

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  7. Re: "I think a broad spectrum antiviral could be dangerous."

    We are not proposing broad-spectrum anti-virals. More targeted ones.

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  8. According to the article, the drawback to the targeted approaches seems to be that antivirals for specific viruses take a long time to develop. Plus viruses mutate very quickly so are likely to adapt even faster than bacteria outwit antibiotics. Plus you have to keep taking the antivirals indefinitely or the virus takes over again (which from a glass-half-full point of view would be an incentive for big pharma).

    In the article, they describe several potential approaches that aren't tied to a particular virus and that would eradicate the threat from the virus once and for all.

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