Researcher - Multiple Sclerosis Is Not an Immune Disease

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Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby paulmur » Wed Jan 04, 2012 8:26 am

Another piece to the puzzle? This is very interesting.

http://www.medicalnewstoday.com/releases/239651.php

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.
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby CureOrBust » Wed Jan 04, 2012 6:03 pm

I think I read this theory somewhere else on the site, with the question as to why then Statins do not work better than they do? I would also of expected to have found a link between high cholesterol and MS as they have with atherosclerosis. I am certain they would of been able to have done a similar study of insurance data that was performed with MS and gout.
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby cheerleader » Wed Jan 04, 2012 9:00 pm

I've been reading up a bit more, and like Cure, the first thought was...hmmm...why don't statins work better if MS is all about lipids? But the theory is more complex. She believes that it is the PPAR--peroxisome proliferated activator-receptors--that are malfunctioning and releasing toxins and oxidants into the endothelial layer. So, it's not just about measuring cholesterol (although that is one indicator of a PPAR problem) And kind of like what I've been writing about in terms of endothelial dysfunction, there are A LOT of different things that can interfere with PPARs--like EBV, vitamin D deficiency, fatty foods, stress, etc. And it's probably a combo platter of all of these environmental issues, plus a PPAR disorder which combine to create MS. I really, really hope she contacts Dr. Cooke at Stanford. I sent her his info. He's presenting new research on MS and the endothelium in Orlando in February, and this is right up his alley, (so to speak.)

For a good basic primer of PPARs and lipid metabolic diseases, check out this paper. It helped me get a better grasp on how metabolic diseases work, and how one could envision MS as a metabolic disorder...
http://endo.endojournals.org/content/14 ... 1.full.pdf


But here's my thought...if PPARs are malfunctioning in someone with MS, why is it a venocentric disease? Why are plaques perivenule? Why are the jugular and azygos veins implicated, but not carotid artery? Wouldn't a PPAR metabolic disease look more like vasculitis, where both arteries and veins are affected? I can't understand why she discounts CCSVI so completely (and believe me, she does...we've corresponded.)

I hope this gets more research looking at MS and the vasculature-
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby MrSuccess » Wed Jan 04, 2012 11:10 pm

..... trauma that requires massive cell repair .....

anyone else find that statement interesting ?


Her words ... not mine.



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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby se1956 » Thu Jan 05, 2012 1:25 am

If one looks into the linked paper from cheerleader

http://endo.endojournals.org/content/14 ... 1.full.pdf

one can see in the images that the liver plays an important role in the metabolism chain.


So again:

After a liver transplant the EDSS of a woman decreased from 5 to less than 2.
After 3 years she was symptom free – completely cured(?).

Therefore a small liver transplant study should be done.

CCSVI may be the result of this faulty metabolism.

R
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby CureOrBust » Thu Jan 05, 2012 3:39 am

se1956 wrote:After A liver transplant the EDSS of a woman decreased from 5 to less than 2.
After 3 years she was symptom free – completely cured(?).

Therefore a small liver transplant study should be done.
After ONE case? really? Maybe research to see if it has happened before or since.
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby se1956 » Thu Jan 05, 2012 7:17 am

Because this one case is so outstanding, a small study should be done - let's say with 10 pwMS (EDSS>5).

It will be hard to find many other cases with EDSS 5 to symptom free after 3 years.

R.
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby masci » Thu Jan 05, 2012 11:14 am

"CONCLUSIONS: Combination immunosuppression with tacrolimus may have a beneficial effect on MS although an effect of donor allograft itself can not be excluded."
http://www.ncbi.nlm.nih.gov/pubmed/15595263
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby se1956 » Fri Jan 06, 2012 3:55 am

Thanks for this link.

"CONCLUSIONS: Combination immunosuppression with tacrolimus may have a beneficial effect on MS.”
reflects the mainstream thinking.

The phrase
….beneficial effect on MS …
is misleading, because the result was extremely positive.

So, immunosuppression with tacrolimus should be a very effective treatment for MS, but it isn't.

Therefore the new liver itself (donor allograft) seems to be the key for this more or less cure.

This is from 2004, it would be very interesting to know how this woman is doing today.

R.
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby CureOrBust » Fri Jan 06, 2012 5:46 am

se1956 wrote:Because this one case is so outstanding, a small study should be done - let's say with 10 pwMS (EDSS>5).
Are you suggesting 10 people with MS, and perfectly fine livers (by current medical knowledge) should have their livers removed, and then 10 livers from others should be implanted, ahead of 10 other people with failing livers, who's lives depend on it? I am guessing there would currently be a shortage of donors? And I am sure the operation is not without high risks. I think a little more research needs to be performed before this should or will happen to humans (I am not suggesting mice!).

se1956 wrote:Therefore the new liver itself (donor allograft) seems to be the key for this more or less cure.

Still a streatch with one example, however a good example of a possible check; ie has this ever happened with any other internal organ transplants?
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby se1956 » Sat Jan 07, 2012 2:33 am

You are right, there are many problems and open questions for such a study.

But if such a study would show that some pwMS are cured, that would be one of the hugest steps in MS research ever.

R.
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby Bethr » Tue Jan 10, 2012 3:33 pm

Liver Transplantation can cure AIP (Acute intermittent Porphyria, a genetic/environmental disease).
The Porphyrias are often misdiagnosed as MS and have many similar symptoms. It could be as simple as that.
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby se1956 » Fri Jan 13, 2012 3:36 am

That's interisting.

I am not an expert, but is seems that from time to time there are no recipients found for donor organs.

In a study with an appropriate database one could try to match such a liver to someone with MS.

I think there would be enough MS volunteers (EDSS>5) for a liver transplant study.

R.
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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby se1956 » Mon Jan 16, 2012 6:27 am

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Re: Researcher - Multiple Sclerosis Is Not an Immune Disease

Postby Cece » Mon Jan 16, 2012 10:17 am

I am thinking: first, do no harm.
Unless there is more support for the thought that the liver transplant is what helped the patient, and not the immunosuppressives or the health improvements from going from a failing liver to a healthy one, I would not expect an IRB to approve this one.
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