Any possibility of new forum: Hypothesis – MS Not Autoimmune

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Any possibility of new forum: Hypothesis – MS Not Autoimmune

Postby lyndacarol » Mon Jan 10, 2011 4:50 pm

Could a forum entitled something like "Hypothesis: MS is Not an Autoimmune Disease" be established so that links to PDF files of full text articles by Peter O. Behan, Chaudhuri, Bruce Trapp, John Prineas, Michael Barnett, and any others could be in one place for easy retrieval?

Does anyone here think this would be a good idea?

Example of possible first file sticky:

1. Behan, Peter O., "Futility of the Autoimmune Orthodoxy in Multiple Sclerosis Research":

http://www.expert-reviews.com/doi/pdf/10.1586/ern.10.69
Possible second post:

2. Chaudhuri: "Multiple Sclerosis is not an Autoimmune Disease" --in Archives of Neurology, a comment (The following link only supplies the first 150 words to the article. I know someone here has the PDF file of the full text.)

http://archneur.ama-assn.org/cgi/content/extract/61/10/1610

3. "Pathogenesis of multiple sclerosis: The eyes only see what the mind is prepared to comprehend" by Bruce Trapp, PhD of the Department of Neurosciences Lerner Research Institute Cleveland Clinic Foundation --an editorial from the Annals of Neurology, Vol. 55, Issue 4, Pages 455-457, (published online 22 Mar 2004)

(I do not have a PDF file for this editorial; anybody?)
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Postby BioDocFL » Mon Jan 10, 2011 7:23 pm

That's an excellent idea. I'll try to come up with some articles for it too. We might want to cover the shortcomings of EAE as a model for MS, if that hasn't already been covered.

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Postby scorpion » Tue Jan 11, 2011 6:56 am

I think it would be better than discussing this hypothesis in the general forum. I am sure the biodoc, uprightdoc, and Dr. Embry would have lots to share in this forum. Isn't there an uprightbeddoc too??? If so my apologies because I certainly do not want to exclude anyone.
Last edited by scorpion on Tue Jan 11, 2011 11:05 am, edited 1 time in total.
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Postby sou » Tue Jan 11, 2011 7:04 am

It is a great idea! it would be a perfect place for gathering all faithless guys and burn them when the time comes!

Seriously, it would be great if we gathered all scientific evidence against the autoimmune hypothesis (yes, it is nothing more than an unproven hypothesis) in one place.

+1 from me, provided that it will be limited to why MS is not autoimmune and nothing more.
Shortest joke: "We may not be able to cure MS but we can manage its symptoms."
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Postby jimmylegs » Tue Jan 11, 2011 7:39 am

it's being discussed. we'll let you know :)
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Postby bettyboop » Tue Jan 11, 2011 12:35 pm

Could a forum entitled something like "Hypothesis: MS is Not an Autoimmune Disease"


Some radical thoughts:
Could a forum entitled something like "Hypothesis: MS is Not an Disease at All"

BB.
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Postby jimmylegs » Tue Jan 11, 2011 6:37 pm

hey there betty, could you please reduce the size of your avatar image to the required limit? thx :)
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Postby rainer » Tue Jan 11, 2011 8:19 pm

Do not like the idea of balkanizing the forum further by beliefs.
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Postby lyndacarol » Tue May 17, 2011 5:18 pm

With the permission of sou, I have abbreviated and edited the following April post of his, which I thought was appropriate for this thread as well:


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Posted: Thu Apr 28, 2011 7:39 pm Post subject:

--------------------------------------------------------------------------------

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.

I don't know [what] is the cause of MS, 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.

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


I certainly appreciate sou's efforts and thoroughness in compiling these references; thank you, sou. I contacted Michael Barnett about posting his papers, but have not had a response. Does anyone have access to the article,The pathology of multiple sclerosis: a paradigm shift. Current Opinion in Neurology 2006 Jun, listed in sou's #2 entry?
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Re: Any possibility of new forum: Hypothesis – MS Not Auto

Postby lyndacarol » Sun Feb 12, 2012 1:00 pm

For #4 in my initial post to this thread or for #10 in sou's list, I propose the following article: http://www.medicalnewstoday.com/releases/239651.php

Researcher Contends Multiple Sclerosis Is Not A Disease Of The Immune System
03 Jan 2012

An article published Friday Dec. 23 in the December 2011 issue of The Quarterly Review of Biology argues that multiple sclerosis, long viewed as primarily an autoimmune disease, is not actually a disease of the immune system. Dr. Angelique Corthals, a forensic anthropologist and professor at the John Jay College of Criminal Justice in New York, suggests instead that MS is caused by faulty lipid metabolism, in many ways more similar to coronary atherosclerosis (hardening of the arteries) than to other autoimmune diseases.

Framing MS as a metabolic disorder helps to explain many puzzling aspects of the disease, particularly why it strikes women more than men and why cases are on the rise worldwide, Corthals says. She believes this new framework could help guide researchers toward new treatments and ultimately a cure for the disease.

Multiple sclerosis affects at least 1.3 million people worldwide. Its main characteristic is inflammation followed by scarring of tissue called myelin, which insulates nerve tissue in the brain and spinal cord. Over time, this scarring can lead to profound neurological damage. Medical researchers have theorized that a runaway immune system is at fault, but no one has been able to fully explain what triggers the onset of the disease. Genes, diet, pathogens, and vitamin D deficiency have all been linked to MS, but evidence for these risk factors is inconsistent and even contradictory, frustrating researchers in their search for effective treatment.

"Each time a genetic risk factor has shown a significant increase in MS risk in one population, it has been found to be unimportant in another," Corthals said. "Pathogens like Epstein-Barr virus have been implicated, but there's no explanation for why genetically similar populations with similar pathogen loads have drastically different rates of disease. The search for MS triggers in the context of autoimmunity simply hasn't led to any unifying conclusions about the etiology of the disease."

However, understanding MS as metabolic rather than an autoimmune begins to bring the disease and its causes into focus.

THE LIPID HYPOTHESIS

Corthals believes that the primary cause of MS can be traced to transcription factors in cell nuclei that control the uptake, breakdown, and release of lipids (fats and similar compounds) throughout the body. Disruption of these proteins, known as peroxisome proliferator-activated receptors (PPARs), causes a toxic byproduct of "bad" cholesterol called oxidized LDL to form plaques on the affected tissue. The accumulation of plaque in turn triggers an immune response, which ultimately leads to scarring. This is essentially the same mechanism involved in atherosclerosis, in which PPAR failure causes plaque accumulation, immune response, and scarring in coronary arteries.

"When lipid metabolism fails in the arteries, you get atherosclerosis," Corthals explains. "When it happens in the central nervous system, you get MS. But the underlying etiology is the same."

A major risk factor for disruption of lipid homeostasis is having high LDL cholesterol. So if PPARs are at the root of MS, it would explain why cases of the disease have been on the rise in recent decades. "In general people around the world are increasing their intake of sugars and animal fats, which often leads to high LDL cholesterol," Corthals said. "So we would expect to see higher rates of disease related to lipid metabolism - like heart disease and, in this case, MS." This also explains why statin drugs, which are used to treat high cholesterol, have shown promise as an MS treatment.

The lipid hypothesis also sheds light on the link between MS and vitamin D deficiency. Vitamin D helps to lower LDL cholesterol, so it makes sense that a lack of vitamin D increases the likelihood of the disease - especially in the context of a diet high in fats and carbohydrates.

Corthals's framework also explains why MS is more prevalent in women.

"Men and women metabolize fats differently," Corthals said. "In men, PPAR problems are more likely to occur in vascular tissue, which is why atherosclerosis is more prevalent in men. But women metabolize fat differently in relation to their reproductive role. Disruption of lipid metabolism in women is more likely to affect the production of myelin and the central nervous system. In this way, MS is to women what atherosclerosis is to men, while excluding neither sex from developing the other disease."

In addition to high cholesterol, there are several other risk factors for reduced PPAR function, including pathogens like Epstein-Barr virus, trauma that requires massive cell repair, and certain genetic profiles. In many cases, Corthals says, having just one of these risk factors isn't enough to trigger a collapse of lipid metabolism. But more than one risk factor could cause problems. For example, a genetically weakened PPAR system on its own might not cause disease, but combining that with a pathogen or with a poor diet can cause disease. This helps to explain why different MS triggers seem to be important for some people and populations but not others.

"In the context of autoimmunity, the various risk factors for MS are frustratingly incoherent," Corthals said. "But in the context of lipid metabolism, they make perfect sense."

Much more research is necessary to fully understand the role of PPARs in MS, but Corthals hopes that this new understanding of the disease could eventually lead to new treatments and prevention measures.

"This new framework makes a cure for MS closer than ever," Corthals said.

Angelique Corthals, "Multiple Sclerosis (MS) is not a disease of the immune system," The Quarterly Review of Biology 86:4 (December 2011).
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References:
University of Chicago Press Journals
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University of Chicago Press Journals. "Researcher Contends Multiple Sclerosis Is Not A Disease Of The Immune System." Medical News Today. MediLexicon, Intl., 3 Jan. 2012. Web.
12 Feb. 2012. <http://www.medicalnewstoday.com/releases/239651.php> APA
University of Chicago Press Journals. (2012, January 3). "Researcher Contends Multiple Sclerosis Is Not A Disease Of The Immune System." Medical News Today. Retrieved from
http://www.medicalnewstoday.com/releases/239651.php.
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