This Is MS Multiple Sclerosis Knowledge & Support Community

You generally hear EAE Mouse Model studies derided at this site, often for very good reason, usually because of the problem of transferring study benefits to humans and MS.

But, several very nice aspects of these studies come to mind:

1. There is no placebo effect to consider.
2. There is no anecdotal discussion involved.
3. Studies results do not depend on subjective symptoms.
4. No Facebook page, or related internet phenomena.
5. No YouTube Pre- and Post-Treatment videos.
6. No Us-vs-Them arguments.
7. No Neurologist/big-pharma conspiracy theories.

--Tracy

Hey - I've got nothing against mouse models...but better to use Dr. Thanaporn's CCSVI mouse model (developed at Stanford) if you're researching MS.

After having experienced the human disease that most closely resembles EAE which is acute disseminated encephalomyelitis (ADEM), I can tell you that this is similar to acquiring years of MS disability in one month.

30% of people with ADEM go on to acquire additional relapses (though not as severe as the first) in what is called recurrent ADEM. Eventually, MS is finally diagnosed if the relapses continue, which is my case.

It should be noted that there are some vairants of EAE that are recurrent in the same way as ADEM is.

The mainstream medical community recognizes that ADEM, MS as well as other disorders have similiar characteristic. They all fall under the category of Idiopathic inflammatory-demyelinating diseases of the central nervous system.

http://www.springerlink.com/content/80mr5u7q23612244/

So in my view (as well as almost all scientist in the field), EAE is the appropriate animal model that closely mimics MS.

CVfactor wrote:EAE is the appropriate animal model that closely mimics MS.

Even if it is a model of MS, which I really doubt, it is still a pretty bad one and practically useless. Better animal models are needed, or better, animal models are needed.

For those of you with any critical thinking skills left, here is a good review article on EAE as a model for MS:

http://www.acnr.co.uk/JF07/ACNR_JF07_review_model.pdf

This is not something that promotes "big pharma" because it bashes a lot of the drugs that were developed by using EAE as a model for MS.

In my view its well written and unbiased unlike this forum.

CVfactor – I find your innuendos offensive:

For those of you with any critical thinking skills left,…

In my view its well written and unbiased unlike this forum.

If you find this forum and its members so obviously unacceptable, I suggest you make your contributions elsewhere.

After further reflection, I apologize to this community of members at ThisIsMS for posting an inappropriate idea that has no connection to MS. My focus should be on aspects of the disease. I let my emotions take control; I hope I will not let it happen again.

lyndacarol wrote:CVfactor – I find your innuendos offensive:

For those of you with any critical thinking skills left,…

In my view its well written and unbiased unlike this forum.

If you find this forum and its members so obviously unacceptable, I suggest you make your contributions elsewhere.

Frankly Lyndacarol, I could care less about your opinions.

CVfactor wrote:In my view its well written and unbiased unlike this forum.

But as useless as the EAE model. You can't make a model of a disease you have no idea what is about. I would be happier if the effort and money wasted on EAE were spent on investigating the cause, not the effect, of MS.

The biased,

sou

I think this is the point of the article. Next time you might want to actually read it before replying.

The key take-away is that most drug developers are trying to make drugs to prevent EAE onset. Instead, the authors believe this is the wrong approach. The correct use of the EAE model is to develop drugs to switch off the immune response once it has been triggered.

But for the plugged vein fanatics, none of this is relevant anyway.

I think you misunderstood what I have written:

What I am asking is that they first have to prove that there is an abnormal immune response, then find out why it exists and then find a method to model it.

Nothing of the above has happened and money keeps being wasted. I am not talking about drugs. I am talking about fundamental errors: Design a model for something there is no proof of existence. What does CCSVI have to do with that?

The fanatic, biased,

sou

PS: I have read the full article.

From my point of view (and many others in the scientific community), it has been shown that MS and MS spectrum diseases are caused by a dysfunction in the regulatory T Cell function.

There is a mountain of evidence both supported with and without animal models (regulatory T-cells are dysfunctional in people with auto-immune diseases because they can directly quantify this!). This is now beyond a hypothesis and has entered the realm of theory. The goal now is how do we restore immune tolerance.

In regards to CCSVI, I just don't see how a restriction in blood flow is going to cause an immune response on your own tissues.

If it is not an immune dysfunction, then what is causing scar tissue in the CNS?

So, please explain how CCSVI causes brain and spinal cord lesions (mainly confined to white matter), is geologically dependent and why viral influences seem play a role.

When I say explain, I mean provide some sort of evidence from people working on the basic science. I'm not talking anecdotal results, or hunches by vascular doctors.

CVfactor wrote:From my point of view (and many others in the scientific community), it has been shown that MS and MS spectrum diseases are caused by a dysfunction in the regulatory T Cell function.

Has it? Where is the proof and which is the auto-antigen?

CVfactor wrote:There is a mountain of evidence both supported with and without animal models (regulatory T-cells are dysfunctional in people with auto-immune diseases because they can directly quantify this!). This is now beyond a hypothesis and has entered the realm of theory. The goal now is how do we restore immune tolerance.

If MS were autoimmune. Remember, we have not proven it yet.

In regards to CCSVI, I just don't see how a restriction in blood flow is going to cause an immune response on your own tissues.

If it is not an immune dysfunction, then what is causing scar tissue in the CNS?

Gliosis is a normal process following damage. Why should the damage be necessarily caused by the immune system?

So, please explain how CCSVI causes brain and spinal cord lesions (mainly confined to white matter), is geologically dependent and why viral influences seem play a role.

When I say explain, I mean provide some sort of evidence from people working on the basic science. I'm not talking anecdotal results, or hunches by vascular doctors.

Let us not involve CCSVI to this discussion. Ask these questions to the CCSVI part of the forum. However, I would start by the Behan's and Chaudhuri's papers and articles, then move to Henderson and Prineas' studies finding no T cell involvement in newly forming lesions and finding astrocyte damage preceeding demyelination and then move to the perfusion studies.

So, I have already created a thread on my point of view under the Natural Approach section.

I have provided links to over 30 studies from reputable journals on this subject with a summary of what I found significant.

There are many more available, but if one is interested in MS and its cause they probably should investigate this aspect and decide for themselves.

So, it looks like you could only come up with four sources on your own (without links of course) to support your point of view, but managed to not answer any of my questions.

Is it the number of sources that counts to you? Did you think that it might happen not to have the time or motivation to prepare a lecture to convince you?

I don't have to prove that MS is not autoimmune. Science has to prove to me that MS is autoimmune. So far, it hasn't. I want proof about which protein is the antigen of the (unproven so far) immune attack.

Once again, leave CCSVI out of the discussion. It's you who involved it, not me. I don't know whether it is the cause of MS or not, but certainly it can't be autoimmune, based on what we know so far.

Anyway, you may start here. The list is far from complete, but I think it supports my opinion enough. I don't have any time for arguing. I demand that you stop speaking personally (CCSVI fanatic etc). I don't mind but it is bad for the discussion, the forum and your "karma". Happy reading!

1. Behan PO, Chaudhuri A. THE PATHOGENESIS OF MULTIPLE SCLEROSIS REVISITED. JR Coll Physicians Edinb 2002;32:244–265.
http://www.meldpuntgezondheidenmilieu.n ... en-mcs.pdf

2. Barnett MH, Sutton I. The pathology of multiple sclerosis: a paradigm shift. Current Opinion in Neurology 2006 Jun;19(3):242-247.[cited 2011 Apr 7 ]
<requires subscription>

3. Juurlink BH. The multiple sclerosis lesion: initiated by a localized hypoperfusion in a central nervous system where mechanisms allowing leukocyte infiltration are readily upregulated? Med. Hypotheses 1998 Oct;51(4):299-303.[cited 2011 Apr 7 ]
http://www.ncbi.nlm.nih.gov/pubmed/9824835

4. Rare PU. Distribution Focal, regional or diffuse Multifocal; as a rule entire central nervous system is affected in chronic MS Age of lesions Always same and uniform Always of different ages (both in acute and chronic MS) Size of lesions 0.1–1.0 mm 1.0 mm or less to 5+ cm Relation of lesions to. JR Soc Med 2005;98:303–306.
http://www.ncbi.nlm.nih.gov/pmc/article ... 980303.pdf

5. Filippi M, Rocca MA. MRI evidence for multiple sclerosis as a diffuse disease of the central nervous system. J. Neurol 2005 Nov;252 Suppl 5:v16-24.[cited 2011 Apr 4 ]
http://www.ncbi.nlm.nih.gov/pubmed/16254697

6. Behan PO, Chaudhuri A. The sad plight of multiple sclerosis research (low on fact, high on fiction): critical data to support it being a neurocristopathy. Inflammopharmacol 2010 Sep;18(6):265-290.[cited 2011 Apr 7 ]
http://www.springerlink.com/content/y352380v17u17r4j/

7. Chan A, Decard BF, Franke C, Grummel V, Zhou D, Schottstedt V, Toyka KV, Hemmer B, Gold R. Serum antibodies to conformational and linear epitopes of myelin oligodendrocyte glycoprotein are not elevated in the preclinical phase of multiple sclerosis. Mult. Scler 2010 Oct;16(10):1189-1192.[cited 2011 Apr 7 ]
http://www.ncbi.nlm.nih.gov/pubmed/20685767

8. Swank RL, Roth JG, Woody DC Jr. Cerebral blood flow and red cell delivery in normal subjects and in multiple sclerosis. Neurol. Res 1983;5(1):37-59.[cited 2011 Apr 4 ]
http://www.ncbi.nlm.nih.gov/pubmed/6140655

9. Ceccarelli A, Filippi M, Neema M, Arora A, Valsasina P, Rocca MA, Healy BC, Bakshi R. T2 hypointensity in the deep gray matter of patients with benign multiple sclerosis. Mult. Scler 2009 Jun;15(6):678-686.[cited 2011 Apr 7 ]
http://www.ncbi.nlm.nih.gov/pubmed/19482861

O.K. Sou, I appreciate you providing this information. So it will take me some time to read it over.

So when I first came to the Forum I new nothing about CCSVI, but I quickly found out just by reading a lot of posts that many people get upset if the CCSVI hypothesis is challenged.

This seems to be ground zero for the CCSVI movement and I am still unclear how it answers my basic questions posted above.

So if anyone has specifics to how CCSVI is related to the following, I would be interested supporting data:

1. Why does CCSVI target white matter tissue and cause demeylination in the CNS? If this is the case it seems logical that this phenomena would be similar in other parts of the body in which their is a problem with blood flow.

Also It has been shown that healthy people also have CCSVI. Why don't they acquire MS?

2. How does CCSVI cause acute forms of demeylinatng diseases?

3. Why would CCSVI be latitude dependent as seems to be the case for MS.

4. How does the dormant virus theory play a role in CCSVI?