Tuesday, 12 January 2016

CrowdSpeak & ResearchSpeak: EBV and MS disease clusters

Could MS be caused by a mutant form of EBV? #MSResearch #CrowdSpeak #CrowdacureMS

"Most slow, or delayed, viral infections of the brain that result from being infected by common viruses are caused by mutant strains of the virus. For, example subacute sclerosing panencephalitis (SSPE) is due to a mutant measles virus. Similarly, a mutant strain of the John Cunningham Virus (JCV) causes progressive multifocal leukoencephalopathy (PML). It has therefore been proposed by many that may be MS is caused by a mutant, or specific, strain of EBV. Is there any evidence for this? No not at present. However, you may be interested to know about a mini-epidemic of MS that occurred in a small semi-rural Danish community in the 90's. Eight school mates developed MS in a cluster were all infected with the same EBV subtype that differed to the EBV subtype in EBV seropositive controls. The odds of this happening are quite remote, not to mention the odds of eight schoolmates developing MS as part of a temporal (time) and geographical (place) cluster. The background to this comment is that the members of  the cluster had all lived in a small community with 74 single-family houses located within an area of 2.7km2. During a 13-year period they had attended the same elementary school with 70-80 pupils for 7 years. The school had a total of 145 pupils during this period. All members of the cluster had been scouts together. Two cases were siblings and two were an aunt and nephew, but MS had not been observed in any of the ancestors of the 8 cases or among the school teachers."

"Could a mutant EBV virus that infected these children have caused their MS as well? One could argue that one cluster of this nature could have occurred by chance. I agree, but it should not be ignored and should be put into the context of several other MS clusters that have been described. Unfortunately, none of the pwMS who were part of these other clusters have had their EBV type studied. This is a great pity."

"This and other data have led many in the field to propose EBV as a potential cause of MS. How EBV causes MS is at present unknown. However an important clue is infectious mononucleosis (IM); people who have IM are more than twice as likely to get MS compared to people who don't have IM. People who don't get infected with EBV are protected from getting MS. This is why we set-up the Charcot Project; its main aim is to investigate the viral hypothesis of MS."


Munch et al. A single subtype of Epstein-Barr virus in members of multiple sclerosis clusters. Acta Neurol Scand. 1998 Dec;98(6):395-9.

OBJECTIVES: Epidemiological studies strongly indicate an infectious involvement in multiple sclerosis (MS). Epstein-Barr virus (EBV), to which all multiple sclerosis patients are seropositive, is also interesting from an epidemiological point of view. We have reported a cluster of MS patients with 8 members from a small Danish community called Fjelsø. To further evaluate the role of EBV in MS we have investigated the distribution of EBV subtypes in cluster members and in control cohorts.

MATERIALS AND METHODS: Blood mononuclear cells were isolated from cluster members, unrelated MS patients, healthy controls, including healthy schoolmates to the Fjelsø cluster patients and finally from persons with autoimmune diseases in order to investigate the number of 39 bp repeats in the EBNA 6-coding region in the EBV seropositive individuals.

RESULTS: We observed a preponderance of the subtype with 3 39 bp repeats in the EBNA 6-coding region both in the MS patients and the healthy controls. In the Fjelsø cluster all 8 cluster members were harbouring this subtype, which is significantly different from the finding in healthy controls (n = 16), which include 8 schoolmates to the cluster members and 8 randomly selected healthy persons (Fischer's exact test P = 0.0047), and also compared to all non-clustered individuals studied (P = 0.017).

CONCLUSION: Infection with the same subtype of EBV links together the 8 persons from the Fjelsø cluster who later developed MS. This finding adds to the possibility that development of MS is linked to infection with EBV.

"As part of Charcot Project 2 we will use viral shedding of EBV as a readout for antiviral drugs targeting EBV. The first drug we will investigate is famciclovir. We propose seeing if it suppresses viral shedding in the saliva and whether it has any utility in treating IM. Please note we can't take Charcot Project forward without generating our own data on EBV shedding in the saliva. Having our own data will allow us to do accurate power calculations for our proposed clinical trials and will hopefully allow us to convince grant reviewers' that we have all the necessary lab assays working. This is why we are asking you to help us raise the money to do the lab work for this study. I sincerely hope you can help."

"If everyone who visited our site donated £1 will get to our target within a week. As always I would like to thank those of you who have already donated so kindly. Thank you."

Click here to find out more!

"If this work inspires you please send the link to anyone you know who has a personal link with MS. I can't tell you how important it is for us not give up on the viral hypothesis of MS. I have a dream, a dream of a world free of MS; the Charcot Project is our attempt at making that dream come true."


CoI: Team G will be recipients of a grant from Crowdacure to perform this research

9 comments:

  1. Did you discuss about Geneuro? They look quite active publication wise (http://www.sciencedirect.com/science/article/pii/S01655728153009890 see this publication that will be published in Feb) Their GNbAC1 therapy is full of promess (at least it is safe). And their work is compatible with the viral hypothesis.

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    1. "Interpreting good, bad and other research news." I guess you could add "But we won't interpret news from a competitor...". They have peer-reviewed publications (many recently), in other words there is something. it might be worth discussing them, no?

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    2. My last comment sounds harsh, but this is because I very much like your blog and your work in general. You give hope to MSers like me and I fully support your initiatives!

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    3. You are wrong. It is not about not interpreting the competitors, it is not supporting their share price. When companies want investment they put out news stories and many blogs pick it up and say listen to this wonder cure on website X. It drives potential investors to the website.

      However when something useful about this molecule is published then we will comment on it, however a paper about some testing unrelated to actual testing in disease e.g. pharmacokinetics is surely not of any real interest?

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    4. FYU ProfG down under has been in contact with the competitors..we all want the same thing - something that works

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  2. This quote from their last article's intro is particularly cool. "Interestingly, certain exogenous viral agents can trigger the reactivation of MSRV copies, particularly Herpesviridae which have been often associated with MS epidemiology without demonstrating a causative role in the disease. Thus, reactivation of silent MSRV, which exhibits pathogenic properties, by such environmental infectious agents may be the missing link between environment and MS onset (Perron and Lang, 2010)."

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  3. Slides 11 and 12 are contradictory. "Did you know there are no licensed treatments for IM.......We hypothesize that preventing or treating IM will lower the incidence of MS". Preventing of EBV means vaccine development. Why are anti-virals not licensed for acute EBV? Because it is self-limiting?

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  4. My first symptom was an optic neuritis and the only thing noticable found in my blood were increased EBV titers and slightly increased HHV6. Since then I suspected Herpes Viruses to play a part in initiating disease.

    With the latest discoveries regarding the gut microbiome I'm wondering how to bring all those pieces together.

    There was an interesting publication last year about short chain fatty acids (SCFA) produced in your gut from dietary fiber and how important these SCFA are for a working brain immune response (e.g maturation of microglia)
    http://www.nature.com/neuro/journal/v18/n7/abs/nn.4030.html

    Maybe the first step is a bad diet with e.g low dietary fiber that "sets an immune status" in the brain that makes it possible for Herpes viruses such as EBV to replicate or initiate an immune response by attracting other immune cells from the blood..

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