This Is MS Multiple Sclerosis Knowledge & Support Community

Dear all,

I was interested to read the research on the front page. I think it was earlier this week that I posted some comments by my good neuro (one of the UK's top MS researchers), that he considered that the problem was that the myelin making cells were damaged / killed because they were in a "sick micro-environment". I assume (my view) that the sick micro-environment might be due to a virus or some other agent (e.g. gamma-interferon). Inflammation then follows which causes further damage etc.

I like the position set out in the research - it make more sense to me that the immune system waking up one morning and saying "lets attack some myelin". The term molecular mimicry never quite cut it with me.

The aim must be to address what is killing / damaging the myelin making cells which in turn should prevent the immune system getting involved etc etc. It might explain why the CRAB drugs are only partially effective.

Lets hope this research gathers pace and leads to some different treatments.

Ian

Thanks Ian. Here's a link to the article Ian refers to:

Possible Shift in Thinking about how Multiple Sclerosis Develops

I may be missing something here but I thought many people connected with this site and various researchers/medical practitioners around the world already thought along the lines of this hypothesis. Isn't that the theory of Cpn? A neuro I saw in Bangkok thought the culprit might be one of 6000 viruses.
Regards,
Phil.

Well, it is still widely accepted among scholars, doctors, schools, and patients that MS is an autoimmune disease-- and the jury, frankly, is still out (it could very well be an AI disease for some portion of MS'ers, as originally conceived).

As with all things multiple sclerosis, we keep an open mind, as do most of the members of our community.

Hi Arron,

Granted.......but the title of the item 'Possible Shift in Thinking....' and Ian's reference to his neuro's views suggests something that may not have been seen before.

Bottom line is that it is good to see some brain-stretching in this area.

Regards,
Phil

Hi Phil,

Bottom line is that it is good to see some brain-stretching in this area.

Regards,
Phil

Yes, the "brain stretching" in this area has been going on for a couple of years now. But this line of thinking has to go up against the long time, established auto-immune theory of MS which has been entrenched in research for over 4 decades. And this established "thinking" has produced some very huge revenue producing "approved" MS drugs! And that is far harder to dislodge than any kind of theory!!

Harry

One of the authors is MH Barnett of Prineas and Barnett fame. He must have been thinking along these lines for quite some time.

Sarah

Hi Sarah,

Anecdote wrote:One of the authors is MH Barnett of Prineas and Barnett fame. He must have been thinking along these lines for quite some time.

Sarah

Mostly since he did that autopsy a couple of years ago on the 17 year old girl who died suddenly from a massive exacerbation. He and Prineas were able to perform this autopsy within 18 hours of her death and they found no evidence of immune system activity in the large lesions on her brain.

Of course they don't know what caused the lesions and this just adds more mystery to MS. But their comments on the lack of immune system involvement did not go well with many of the "established" MS research community.

Harry

I'm very happy, thrilled that folks are out there studying this and learning more new stuff. very excited.

This info seems to explain how MS gets started. Once it's started the auto-immune theory takes over and explains how the body continues to perpetuate the disease. So, while this is great research, I don't see how it helps those who already have MS. I can see where it will help to perhaps create a vaccine for folks who don't have MS. Then again, maybe one could follow up Novantrone with the vaccine and then be MS free. hummmmm.
napay

Doesn't it seem logical in researching a disease to find out in the FIRST step WHAT kind of disease it is? Treating MS for the last half-century as "autoimmune" has gotten us very little progress! I, too, always thought it odd that the immune system would wake up one day and start attacking. (Then there are remissions and relapses--what's with THAT?) Now maybe we're getting somewhere!

I admire those folks in Australia! Barry Marshall learns that ulcers are caused by H. pylori bacteria, not just too much acid and stress; now John Prineas and MH Barnett have started a new way of thinking about MS! The drug industry will give up the autoimmune angle reluctantly since that is what their products target!

I found this news encouraging; I may have to send a copy to my physician (just to make sure he knows about this--he is used to mail from me)!

Yes Lynda Carol, I quite agree, it would definitely be a good thing to find out what kind of disease we have. We know what it’s called but not what it is only that we have it. Fine fix IMO.

About that “sick micro environment”, here’s an interesting (IMO) abstract on the matter. It seems to suggest that the neurodegeneration seemingly evident in MS may not even be totally dependent on the inflammatory process. Modulating Processes within the CNS is Central to Therapeutic Control of MS …

neurodegeneration appears to be at least partially independent from neuroinflammation….. It is likely that immunomodulatory treatments acting purely in the periphery will provide only indirect and not direct neuroprotection…

The pathogenic process in the central nervous system itself should be the major focus in multiple sclerosis therapy in order to protect against demyelination and axonal loss and to promote remyelination and regeneration directly in the target tissue, independently of peripheral immune status. In conclusion, selective treatment strategies aimed at preventing axonal injury within the central nervous system are required to complement existing, peripherally acting treatments targeting the immune system.

For my 2 cents, I still like the idea that one factor in the “sick micro environment” might be glutamate toxicity. The recent front page article suggests damage to the oligodendrocytes happens first and the inflammation follows. This abstract seems to suggest that oligodendrocytes could be susceptible to glutamate toxicity since they have those “NMDA receptors”.

Oligodendrocytes are known to express (Ca2+)-permeable glutamate receptors and to have low resistance to oxidative stress, two factors that make them potentially susceptible to injury…….Previous studies had failed to detect NMDA receptor mRNA or current in oligodendrocytes but three new papers demonstrate NMDA receptor expression in oligodendrocytes.

I’ve no scientific or medical background whatsoever, but I’ve latched onto these NMDA receptors and the notion of “glutamate toxicity” since the little bit I think I might understand seems to support the notion that theoretically it could account for damage to the myelin, axons and neurons in people with MS and be part of a “sick micro-environment”.

The good news is there are several things already on the market that might help minimize it, i.e., the memantine I posted some info about recently, several hormones, and minocycline. I think glutamate toxicity is also part of the thinking about how ldn may work. So, even if MS is not “auto-immune”, and I personally don’t think it is, I’m still optimistic that we could be a lot closer to more effective treatment than we think.

Even if we don’t know what kind of disease it is I do think the researchers may have made some progress in understanding the molecular injury cascade. I'm sure hoping that's the case.

Sharon

I think the item copied below from the MSnews diary of the April 2006 AAN meeting in San Diego is linked to the discussion above. Who is William Sibley? Interesting to see the MS Society heading in this direction.
Phil.

Clinical Trials II (Art and Hollie)

The Dystal Prize

The AAN and MS Society give a prize out each year to a leader in MS research. This year the recipient was William Sibley. He gave a talk on the possibility of MS as a post-infectious disease and viruses as a trigger of MS. He mentioned some interesting findings Art hadn't heard before such as that people with MS have fewer clinically evident infections than controls and that people with more infections seem to progress more slowly (opposite to what you would expect).

Tracking relapses by month, there seem to be peaks in April and August (Art's relapses fall into those months). Also, optic neuritis has a lull in Jan-Mar and peaks in Apr-Jun, which correlates with rhinovirus infections. Sibley mentioned a small study that correlated rhinovirus infections with exacerbations, and said that the study was now being repeated in a larger sample based in Utah and Arizona

Phil--I don't know anything about William Sibley but I found this info interesting.

that people with MS have fewer clinically evident infections than controls and that people with more infections seem to progress more slowly (opposite to what you would expect).

Since we're in a "paradigm shift", here's an abstract on the neuroprotective effect of inflammation

Furthermore, BDNF is expressed in different types of inflammatory cells in brain lesions of patients with acute disseminated leukoencephalopathy or multiple sclerosis. It seems plausible that the immune cell-mediated import of BDNF and other neurotrophic factors into the central nervous system has functional consequences and implications for the therapy of multiple sclerosis and other neuroimmunological diseases.

Wild speculation on my part--maybe people with more infections have more BDNF, therefore they have more neuroprotection and that's why they progress more slowly.

And, here's more info on the general topic of the importance of the CNS in MS. Immunology of MS

an important paradigmatic shift in the study of MS has occurred in the past decade. It is now clear that MS is not just a disease of the immune system, but that factors contributed by the central nervous system are equally important and must be considered in the future.

Take care everyone

Sharon

HarryZ wrote:... he did that autopsy a couple of years ago on the 17 year old girl who died suddenly from a massive exacerbation ...

When I first read this article, it felt like old news. Its interesting that it was the same researchers. And if I am not wrong, they work in the same office as my neurologist. So he can expect a couple of questions on my next visit.

Do we know why this article makes no reference to the earlier work?

Did it take the second example as a justification / proof that it wasnt a random event?