This Is MS Multiple Sclerosis Knowledge & Support Community

Sorry, time to leave the board.

-finn

Not sure why they think it is only one lesion, they studied 12 subjects (abstract doesn't say how many lesions). PubMed entry here:
http://www.ncbi.nlm.nih.gov/entrez/quer ... s=15048884

Sorry, time to leave the board.

-finn

It seems a little inconsistent that we are beginning to talk about MS actually being multiple different diseases, and yet at the same time we feel compelled to determine if MS is or is not an autoimmune disease as if it must be one or the other. What happened to the multiple disease theory? How about this: some of the pathologies that we call MS are indeed autoimmune disorders, and respond very well to the autoimmune therapies; some of the pathologies that we call MS are NOT autoimmune and thus do not respond to the autoimmune therapies. I think progress will proceed fastest if we embrace the idea of multiple disorders and not get struck rtying to put MS into one of two categories. THoughts?

In the past couple of years, some prominent MS researchers have started to say that the autoimmune response in MS patients is a "reaction to" as opposed to a "cause of" damage to the myeline. In other words, something in the MS patient's system is causing the damage and the immune system is reacting to that because of the inflammation that is caused. Usually it's the macrophage cells that end up going to these lesions to "clean up" after the damage.

As to what is causing the original damage....that's the million dollar question and until someone can come up with the answer or answers to that question, treatment for MS patients is going to continue in the haphazard way it has in the past 40 years!

Harry

Understood. But isn't it likely that not all the disorders we call MS have this same process?

billf wrote:Understood. But isn't it likely that not all the disorders we call MS have this same process?

That's a question that nobody has been able to answer and that's all we have is theory after theory at the present time. What's discouraging is that after 50 years of research, the docs still can't even tell us what causes MS or even what kind of disease it actually is!! Unlike other organs in the body, you can't send a probe into the brain and watch what is going on in order to determine this. All of our info comes "after the fact" and thus the multiple theories.

Add the multi-billion dollar drug industry which thrives off the auto-immune theory and you end up with little progress being made in trying to determine the answers to this lousy disease.

Dr. Prineas' work on the autopsy of the young girl who died from MS has certainly changed some long held thinking about the disease but I'm afraid the progress that is needed here is going to take a long time.

Harry

Sorry, time to leave the board.

-finn

Well, I'm certainly way outside that EAE/MRI box. Too bad I'm not a researcher with some scientific background.

I haven’t had an opportunity to check the new links you gave us, but with such a discussion I wanted to weigh in on the topic. And, despite the fact I have no scientific background, I’m still trying to try make the tiniest bit of sense out of all this MS information.

I think I agree with most of your speculation Finn. It sure is fun to speculate. I can personally put my own scenario in your speculation and end up with MS as not auto-immune.

Right now I tend to think of MS as a single disease process with lots of variables influencing whether or not one actually gets it, i.e, genetic predisposition with variable penetration that’s heavily dependent on a host of environmental factors (exposure to sun, viruses, bacteria, etc.). Then, cumulative physiological responses to stress (not psychological)and other hormone shifts finally reach a level and point that allows susceptible brain cells to die, inflammation is ignited and there's now a visible expression of MS as an “inexplicable disease.”

As Harry said though, the real question in my mind now is “what is causing the original damage?” What is prompting the oligodendrocytes to die in the first place?

I’ve already speculated about cortisol. I don’t know if c. pn. in a dormant state would kill oligodendrocytes given the right "stressors". But I have found some information related to the front page article MS Deterioration Reversed with Antibodies and Neuroprotectors (Glypromate/NBQX) that suggests glutamate can kill oligodendrocytes.

The first is Glutamate excitotoxicity in a model of MS by Pitt, D et al from the Albert Einstein College of Medicine, NY, Nat Med 2000 (PMID 10613826)
In this report,

NBQX …resulted in substantial amelioration of disease, increased oligodendrocyte survival, had no effect on lesion size and did not reduce the degree of central nervous system inflammation.

The abstract concludes:

Thus, glutamate excitotoxicity seems to be an important mechanism in autoimmune demyelination, and its prevention with AMPA/kainate antagonists may prove to be an effective therapy for MS.

The second is The link between excitotoxic oligodendroglial death and demyelinating diseases by Matutue, C,, et al from Spain in Trends Neurosci. 2001 (PMID 11250007)

However, acute and chronic alterations in glutamate homeostasis can result in overactivation of AMPA and kainate receptors and subsequent excitotoxic oligodendroglial death. Furthermore, demyelinating lesions caused by excitotoxins can be similar to those observed in MS……indicates that oligodendrocyte excitotoxicity could be involved in the pathogenesis of demyelinating disorders.

Now, I had to look up excitotoxicity to be sure it meant cell death and it does. Check out http://www.alscenter.org/about_als/excite.cfm for a discussion of glutamate and cell death. And, what’s great, per the This is MS article, NBQX is already available. So, it seems to me like NBQX could be a “not auto-immune” neuroprotective treatment of sorts for MS based on this and the New Zealand research. I'm hoping

But, Harry's question remains, “What is causing the original damage?” “What is causing the oligodendrocytes to die?" What are some other possibilities for this?

Take care everyone. Enough for now.

Sharon

(BTW Finn, I tried that URL tag, what a mess , but I haven't given up on that either! )

I just posted a reference to a paper that has an interesting take on MS. It's from 2002 and was widely disputed by those who claim it is an autoimmune disease, but it makes a lot of good points that have never been addressed to my satisfaction:
http://msnews.bostoncure.org/article.pl ... 27/1155216

Sorry, time to leave the board.

-finn

Finn,

[*]Lack of vitamin D(?)
In an American study women who took vitamin D supplements were 40 percent less likely to develop MS, but some researchers have doubted the validity of the study.

I believe that this American study was done by obtaining survey info from a huge group of US nurses (hundreds of thousands). Data from this group is often used to conduct non-scientific studies and was the basis for HRT therapy(Hormone ) for women. HRT therapy, after a few years of use, was found not to be very good. That is why some researchers don't hold too much credibility for the data obtained from this group about vitamin D.

Harry

The Nurses Health Study includes approximately 60,000 nurses. Studies like this one, including the Framingham Heart Study and the Black Woman's Study, are used to do prospective research. I.e. they don't have a particular aim in mind, but hope to see results afterwards by analyzing the data. It's definitely flawed for many study types, but it is often the closest we'll ever get to doing the perfect experiment. The Vitamin D study was done by Alberto Ascherio's group at Harvard. They definitely found a statistical connection, but that does not imply causality, nor did they claim that it did. I've found that the claims made by the scientists usually differ significantly from the reporting of those claims in the papers. Alberto had similar results with EBV using the Nurses study data and that got reported very differently than he wrote it up (much stronger claims in the papers).
I usually try to contact the researchers or at least read the original paper before passing judgement (but sometimes I pass judgement indiscriminately) as you often find the claims made in the paper are quite fair, but less intriguing than those in the newspaper.

More speculation from a very personal view.

I'm half Asian (more on that under genetics), half Italian and spent the first 8 years of my life in India. Lots of sunshine and possibly rules out environment too! There is no history of MS in my family. I have had various horribly expensive tests done for food intolerances/leaky gut etc and the only thing I am 'slightly' intolerant to is coconut, which I have hardly ever touched.

I was brought up vegetarian but started eating fish when I was 9. I absolutely detest milk and cheese and haven't touch either since I was about two. I have eaten organic food since I can remember and never touch junk food. I have never had measles, chicken pox, glandular fever, been in a car accident or even broken a bone.

So I don't fit in to the majority of the various theorectical categories. So I think MS may be a syndrome not a single disease. This may also explain the great variation in its course. What causes MS? I haven't got a clue but I can understand the process and have never thought it an autoimmune condition.

I think stress can contribute, could possibly be a trigger for flare ups but I don't believe it is the cause of MS for everyone but I'm willing to believe it may possibly be a cause for some people. I think a genetic predisposition also plays a role and may be the only commonality. i think this partially because of the theory Finn mentions about Vikings. I am half parsee and this is the predominant group in India to be affected by MS. And this is linked to those pesky Vikings too. Not entirely convinced but it is interesting as are studies of twins, again ruling in genetic predisposition.

This is an interesting snippet on the Viking theory

'MS is more common in northern Europe than southern Europe. It is also more common in the upper midwestern United States, where many Scandinavians and other northern Europeans went peacefully to live over the past two centuries.

This link between MS and Scandinavian descent got one Harvard professor thinking about the Vikings [4], who used less-peaceful means to spread their genes [7]. Could they be responsible for the concentration of MS in northern European peoples and for the worldwide occurrence of the disease?

To investigate this question, the professor looked at Viking history and found three things:

The Vikings have been known by many names throughout history, including Norsemen, Normans, Danes, and Varangians.

The Vikings did more than just terrorize northern Europe and the north Atlantic -- they and their descendants terrorized most of the world. For example, there are Viking carvings in a mosque in Istanbul (Turkey) and on a statue outside Athens (Greece). There was a Viking regiment in the Chinese Emperor's Imperial Guard in the 1300s, in the service of the eastern Roman empire 300 years earlier, and in the Crusades.

Wherever the Vikings had raided, taken slaves, traded, and settled, there was more MS than in people in nearby areas.
The best example quoted by the professor centers on Palestinian Arabs living in Kuwait. They have about two-and-a-half times more MS than the Kuwaiti Arabs. Historically, Palestinian Arabs originated in the eastern Roman empire near Jerusalem, so we might suspect they carry some Viking genes. However, the professor did something interesting: he looked at the eye color in these MS patients. He found that 62% of the Palestinian Arabs with MS had blue or hazel eyes, whereas 78% of the Kuwaiti Arabs had black or brown eyes. This suggests that the Palestinian patients descended from a "lighter" genetic stock, which, the professor hints, points to the Vikings.

The professor mentions other pockets of MS, such as the Canary Islands and the Parsees in India, and finds historical evidence that Vikings could have been involved.

There has been little comment from the rest of the scientific community about the professor's theories. For now, we should treat it as intriguing, but certainly not proven. Interestingly, modern techniques of genetic research could help sort out the human family tree and test the professor's theory once and for all. '

My research these days is mainly looking in to the role of the specific peptides which traverse the brain and endocrine system. Again though what leads to this has various causes.

Oh well, maybe sometime we may find the answer.

Felly

oops forgot to post the link to the Viking article, which also makes mention that Finns may have a type of MS all to themselves. You lucky man:-)

http://health.discovery.com/minisites/dna/ms.html

Felly