Friday, 8 May 2015

EBV activity correlates with MRI activity

Time to refocus on EBV as a driver of MS disease-activity. #MSBlog #MSResearch

"There are no original ideas! Professor Chris Hawkes has been trying to get a study similar to one described below off the ground for over 3 years. We have funding turned down to do this study, but have recently been given some priming money to do some proof of concept work around the theme of EBV reactivation driving MS disease activity. Now that we have been trumped could we simply quote the paper below? Possibly, but the work is potentially so important it needs to confirmed. In addition, the study below is quite small and is by no means definitive."


"What these investigators have shown is that cells, when taken from the peripheral blood of MSers, are more likely to proliferate spontaneously in culture (so called autologous lymphoblastoid cell lines or LCLs) in MSers shortly before they show new lesions on MRI. The LCL phenomenon is due to EBV immortalising cells in culture and is a marker of EBV activity. This study hints that a loss of control of EBV in the peripheral blood precedes the onset of new disease activity as measured on MRI. Interesting? Yes, very interesting. Is this causal or simply an association? The only way to test this is to use drugs that block EBV viral activity and see if it prevents MRI activity and/or relapses. We proposed doing this study several years ago with an anti-viral drug with good anti-EBV activity and our grants got rejected three times. Interestingly, the grant peer reviews were like Marmite (a British food spread that you either love or hate); some grant reviewers gave us very high scores and others very low scores. This is why we are resorting to crowdfunding to try and get our Artemis trial funded. The Artemis trial will hopefully provide us with the necessary biomarker data to support a more robust grant application in the future. Doing research is becoming increasingly difficult and  taking ever longer to translate ideas. Successful research is about translating ideas into grant funding and testing hypotheses. At the moment we are failing hopelessly."



Epub: Latham et al. Antivirus immune activity in multiple sclerosis correlates with MRI activity.Acta Neurol Scand. 2015. doi: 10.1111/ane.12417.

OBJECTIVE: The objective of this study was to determine whether reactivation of Epstein-Barr (EBV) or activation of the anti-EBV immune response correlates with MS disease activity on MR imaging.

METHODS: Subjects with early, active relapsing-remitting MS were studied for 16 weeks with blood and saliva samples collected every 2 weeks and brain MRI performed every 4 weeks. We isolated peripheral blood mononuclear cells from each blood sample and tested the immune response to EBV, autologous EBV-infected lymphoblastoid cell lines (LCL), human herpesvirus 6 (HHV6), varicella zoster virus (VZV), tetanus, and mitogens. We measured the proliferative response and the number of interferon-γ secreting cells with ELISPOT. We measured the amounts of EBV, HHV6, and VZV DNA in blood and saliva with quantitative PCR. On MRI, we measured number and volume of contrast enhancing and T2 lesions. We tested for correlation between the immunologic assays and the MRI results, assessing different time intervals between the MRI and immunologic assays.

RESULTS: We studied 20 subjects. Ten had enhancing lesions on one or more MRI scans and one had new T2 lesions without enhancement. The most significant correlation was between proliferation to autologous LCL and the number of combined unique active lesions on MRI 4 weeks later. Both proliferation and number of cells secreting interferon-γ in response to LCL correlated with the number of enhancing lesions 8 weeks later.

CONCLUSIONS: We find evidence for correlation of antiviral immune responses in the blood with subsequent disease activity on MRI scans.

6 comments:

  1. Very Interesting News! Many thanks as always, but may I ask you why you speak only about Artemis and not about Charcot/Inspire ? After all Inspire trial results are still unknown, perhaps important...

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  2. In these studies the percentage of seronegative MSers for MS is very low, or it does not exist, ie 100% of the samples had positive serology for EBV?

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    1. As I understand it, pretty much every MSer is seropositive for EBV but also a huge majority of the general population are also seropositive.

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    2. MD2 Thanks! But I read about this possible association of EBV and MS I wondered if the virus would cause an exaggerated response of the immune system in a complex interaction of genetic factors, there are more than 150 genes that would link with MS... And then I asked myself, and isolated cases of MS in families, where only one individual had the disease when looking for other family members, and they also do not have other autoimmune diseases possibly involved?

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  3. Is this a precursor to your charcot trial?
    We know the French are on their way with gbnac1 which I think they disclose their next steps to take the drug forward this month

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  4. Has the crowdfunding started for ARTEMIS? If so, how do we contribute?

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