Monday, 14 January 2013

Research: HERVs increase in MSers/PwMS

#MSBlog: Retroviruses associated with MS differ in males and females. Is this a tantalising clue to MS?

Epub: Garcia-Montojo et al. 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. PLoS One. 2013;8(1):e53623. doi: 10.1371/ journal. pone. 0053623.

BACKGROUND: MS 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 MSers. 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. 


RESULTS:178 MSers (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 MSers 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 MSers (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). 

CONCLUSION: MSRV increases its copy number in PBMC of MSers 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.


"Another tantalising study from the Perron group suggesting that HERVs are associated with MS. It would be great if other groups would start working on HERVs in MS and if someone had the courage to do a a study using an anti-viral targeting HERVs. The real unanswered questions is how does HERVs explain the epidemiology of MS. This includes the changing prevalence, the latitudinal gradient, the association with EBV and vD deficiency, the link with smoking and its interaction with the genetic factors that have been identified to date."

"HERVs and MS may become one of my grand challenges for 2013 and beyond!"

21 comments:

  1. There's a Swiss Biotech company called GeNeuro that's developed a monoclonal antibody targeting HERV. They've launched a phase II clinical trial in MS. Look forward to seeing the results. http://www.geneuro.com/en/news/press_articles.php

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  2. Yeah, just read the release, it's not spam in case you're wondering.

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  3. I posted on this without mentioning the company not so long ago.

    I know that antibodies are a defence against viruses, the question must be where is the site of action required?. If in the peripheral blood that is OK but if it is in the brain will the antibody reach ever its target

    Maybe the trial will tell us.

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  4. Elevated HERV level could be the result of the MS process. The fact that there seems to be a correlation with disability points to that direction. It's strange that you don't mention this possibility.

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  5. Replies
    1. You must have something in mind to explain how exactly does HERV inflicts damage in MS, do you? Until then both probabilities are at least equal.

      If HERVs were anywhere near the cause of MS then more of them should be related to more aggressive MS. But the only relation seen was with MS duration. Therefore HERVs build up as MS goes on.

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    2. Hi VV,

      What would be your approach to dealing with MS?
      vit-d?, ccsvi?, diet?, exercise?, drugs?

      Thank you

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    3. I sort of know what he would not do, but I dont belive he has told us what he would do. I have a suspecion thou that i may be ccsvi

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    4. Anon, the first thing to do is get a clearer view of what MS really is. This can be accomplished by studying unbiased material regarding MS and matching it to your self-perception (this second step can only be undertaken by patients, that's why most doctor will never understand it). Yes, it all has to do with the the fluid balance and flow within the compartment that contains the CNS, brain & spine. It's about both blood and CSF flow. Let's call it ccsvi.

      Once you get convinced about the state of your body, it is quite obvious what you should to. I had 4 blood routes opened, one of them reclosed forever. So i am +3, which has given me a 2 year placebo effect... Drugs are totally out of the question, i never touched them. Exercise is a double-cut knife: if the blood flow is seriously compromised it can cause more damage. Diet is of utmost importance: you need a strong immune system and a fast flowing blood to compensate for flow obstacles. Vit-d? I consider it part of a healthy diet, nothing more than that.

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    5. This stuff is either seriously absurd or seriously brilliant.

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    6. VV, i'm a little surpised about your view on vit-d. At least on this issue i thought you would find common ground with prof g. Please explain.

      What diet gives a strong immune system and fast flowing blood?

      swank? omega-3?

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    7. Vit-d is normally reduced in patients with chronic diseases, as it is the fuel of the immune system. So finding low levels of vit-d in MS patients is rather expected. The vit-d argument has always been used in relation to the observed MS prevalence in colder climates. My view is that it is not the absence of sunlight to blame, but the differences in diet: a cold climate diet usually contains more fat. Moreover, cold climate population receives fewer warm climate DNA "additives" and thus recycles the MS prone genes.

      Swank is a beneficial diet. Add to it some natural blood thinners, ω3, ginkgo biloba, maybe aspirin if your stomach can handle it. Generally, any diet approved for people with cardiovascular disease.

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    8. Re 'Vit-d? I consider it part of a healthy diet'

      Amazingly ignorant statement! A healthy diet won't give you enough Vit D. You have to get it from the sun or take supplements.

      Cold water fish are among the few natural sources of Vit D. In warm climates there is almost nothing.

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    9. Which is why the MS incidence in Northern Norway actually drops compared to the South (the reverse of what is seen in other countries such as France) as they eat a high fish diet rich in Vitamin D.

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    10. MD2, i think you are oversimplifying things. A high fish diet does more than just supplement the necessary vit-d. The most important is the balance between different types of fat. Eating more fish gives you abundance of omega fats and at the same time reduces the consumption of red meat. This type of diet is the best for cardiovascular diseases, and as it happens, the basis of Swank diet.

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    11. "Vit D... is the fuel of the immune system"

      This isn't oversimplifying things?


      "This type of diet is the best for cardiovascular diseases, and as it happens, the basis of Swank diet."

      And?

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    12. There are fish and there are fish with vitamin D. Most farmed fish is fed on fish food and not plankton and other stuff that actually make the vitamin D in wild fish, so farmed fish is not high in vitamin D.

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  6. Studies indicate that residence in a high sunlight area or outdoor work reduce MS mortality, that MS prevalence is inversely correlated with altitude (which relates to sunlight intensity). Unless you're suggesting that those who live up mountains eat a significantly different diet to those in the foothills then your theory doesn't hold water VV.

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    1. Altitude is correlated with mean temperature, and cold climate diet certainly differs from warm climate diet. In any case, there is no way to find the cause of MS by looking at graphs. One has to focus on the specific and unique characteristics of MS that are continuously overlooked.

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  7. the HERV's will probably be in the lymphatic system's B cells. 80% of the lymphatic system is in the gut. i think thats where the inflammation is mostly coming from. HERV env protein cause a lot of problems but maybe this drug will silence it.

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