Myelin repair?

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Myelin repair?

Postby Lars » Fri Jun 08, 2007 3:14 pm

This should open a can of worms. What are thought to be the best ways to promote myelin repair?
Thanks,
Lars
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Postby Lyon » Fri Jun 08, 2007 4:19 pm

A darned interesting can of worms though......

Whew, interesting question.

DIGNAN!!!!!!!

Bob
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Postby dignan » Fri Jun 08, 2007 8:06 pm

OK, I'll bite. I assume you're asking about currently available ways to promote myelin repair. I did a quick look around and found two things that might promote myelin repair: cannabinoids and certain polyunsaturated fatty acids.


Therapeutic Action of Cannabinoids in a Murine Model of Multiple Sclerosis

Angel Arevalo-Martın, Jose Miguel Vela, Eduardo Molina-Holgado, Jose Borrell, and Carmen Guaza
Neuroimmunology Group, Neural Plasticity Department, Cajal Institute, Consejo Superior de Investigaciones Cientıficas, 28002 Madrid, Spain, and Unit of Histology, School of Medicine, Department of Cell Biology, Physiology, and Immunology, Universidad Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain

Theiler’s virus infection of the CNS induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis (MS). Cannabinoids may act as immunosuppressive compounds that have shown therapeutic potential in chronic inflammatory disorders. Using the Theiler’s murine encephalomyelitis virus model, we report here that treatment with the synthetic cannabinoids WIN 55,212–2, ACEA, and JWH-015 during established disease significantly improved the neurological deficits in a long-lasting way. At a histological level, cannabinoids reduced microglial activation, abrogated major histocompatibility complex class II antigen expression, and decreased the number of CD4 infiltrating T-cells in the spinal cord. Both recovery of motor function and diminution of inflammation paralleled extensive remyelination. Overall, the data presented may have potential therapeutic implications in demyelinating pathologies such as MS; in particular, the possible involvement of cannabinoid receptor CB2 would enable nonpsychoactive therapy suitable for long-term use.

To read the entire article: http://www.jneurosci.org/cgi/reprint/23/7/2511



Polyunsaturated fatty acid supplementation stimulates differentiation of oligodendroglia cells.

Dev Neurosci. 2006;28(3):196-208.
van Meeteren ME, Baron W, Beermann C, Dijkstra CD, van Tol EA.
Biomedical Research Department, Numico Research B.V., Wageningen, The Netherlands.

Dietary polyunsaturated fatty acids (PUFAs) have been postulated as alternative supportive treatment for multiple sclerosis, since they may promote myelin repair. We set out to study the effect of supplementation with n-3 and n-6 PUFAs on OLN-93 oligodendroglia and rat primary oligodendrocyte differentiation in vitro.

It appeared that OLN-93 cells actively incorporate and metabolise the supplemented PUFAs in their cell membrane. The effect of PUFAs on OLN-93 differentiation was further assessed by morphological and Western blot evaluation of markers of oligodendroglia differentiation: 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), zonula occludens-1 (ZO-1) and myelin-associated glycoprotein (MAG). Supplementation of the OLN-93 cells with n-3 and n-6 PUFAs increased the degree of differentiation determined by morphological analysis. Moreover, CNP protein expression was significantly increased by gamma-linolenic acid (GLA, 18:3n-6) supplementation.

In accordance with the OLN-93 results, studies with rat primary oligodendrocytes, a more advanced model of cell differentiation, showed GLA supplementation to promote oligodendrocyte differentiation. Following GLA supplementation, increased numbers of proteolipid protein (PLP)-positive oligodendrocytes and increased myelin sheet formation was observed during differentiation of primary oligodendrocytes. Moreover, increased CNP, and enhanced PLP and myelin basic protein expression were found after GLA administration. These studies provide support for the dietary supplementation of specific PUFAs to support oligodendrocyte differentiation and function.

Pubmed URL
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Postby Lyon » Fri Jun 08, 2007 8:11 pm

I knew you'd come through! I've been searching the internet all night with no luck whatsoever!

Thanks dignan!!
Bob
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Postby Lars » Sat Jun 09, 2007 10:29 am

Wow,
You guys are always right on it. So basically fatty acids and getting stoned. I can do that. Now to explain the question, I seem to have finally had some remittance after nearly a year. Overall fatigue and general well being has improved. All this without a single Tovaxin injection yet. 10 weeks and no needle in sight. What hasn't improved is all the parts that have become useless over the same year. I still have almost no use of my right arm and hand (its why my posts are generally short). So I thought it may be time to concentrate on the myelin issue while I have the energy to do so. As always thanks for your support.
Lars
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Postby Lyon » Sat Jun 09, 2007 11:12 am

Hi Lars,

When you get a chance email me at lyonro@msu.edu so that I can reply a file to you.

Actually, I think this is a free file http://tinyurl.com/2lglca (at the bottom of the page select "Full Text HTMS or Full Text PDF")

Thanks,
Bob
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Postby Lars » Sun Jun 10, 2007 7:16 am

Bob,
Thanks. Where do you find this stuff? Fairly wordy but it seems reducing lesions is key before re-myelination can occur, no? Another "yippee" for Tovaxin. We always seem to end up at the stem cell place. Got any pull with the white house?
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Postby Lyon » Sun Jun 10, 2007 10:47 am

Lars wrote:Where do you find this stuff?
Hi Lars,
I guess that's where the "obsession" comes in. Despite the fact that I don't understand a lot of it, I spend my free time finding and reading it.

Lars wrote:Fairly wordy
Most of those peer review articles are as precise as possible specifically because they expect their work and words to be publicly critiqued by their peers.

Lars wrote: but it seems reducing lesions is key before re-myelination can occur, no?
I guess that's why I included the link to the article even though I knew you were looking for things that you could do to preserve and restore myelin right now.

I'm probably not wording this the best because I'm heading to my nephew's graduation open house but 1) at this point I don't think there's anything within your grasp which is proven to promote remyelination....possibly vitamin B12. 2) in the current environment it seems wise to stop the disease process before worrying about remyelination 3) no one has experience with the disease process being stopped and I think you're going to be pleasantly surprised with the amount of natural remyelination 4) due to the above, at least to my way of seeing things, all interest and efforts should instead be directed towards axon regeneration.

Lars wrote: Another "yippee" for Tovaxin.
I agree. It might sound contrary but I'm convinced that Tovaxin can stop the disease process and hopeful that I'm not wrong.

Lars wrote:We always seem to end up at the stem cell place. Got any pull with the white house?
Ha! Don't get me going. I'm counting the days until that lunatic gets evicted from the Whitehouse so that we can see what the next lunatic brings. I've nothing morally against using embryonic stem cells but a lot of people who do have things all tied up. I think it's time to forgo that and find ways to do what we need to with adult stem cells. Things are showing that it's not only possible but in many (important) ways using your own stem cells is better.

Bob
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Postby Lars » Sun Jun 10, 2007 6:54 pm

Amen on the lunatic business! Thanks for your help. We all get caught up in this forum and forget what is ultimately important. Its been a while since I've heard how your wife is doing. Good news I hope.
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Postby Lyon » Tue Jun 12, 2007 7:59 pm

Still very well, thanks Lars. Had her second injection a couple of weeks ago. Kind of like Tim hints, no news is good news!
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Postby finn » Wed Jun 13, 2007 12:39 am

Lars wrote:Fairly wordy but it seems reducing lesions is key before re-myelination can occur, no?

Well, maybe first somebody should find out why lesions occur. What if MS is found to be a neurodegenerative disease and demyelination really would be caused by axonal degeneration (as suggested by some researchers)? In that case halting demyelination and promoting remyelination would have an effect only on reverseable disability. Permanent disability caused by slow neurodegeneration would still progress.

-finn
"The great tragedy of science - the slaying of a beautiful hypothesis by an ugly fact.” -Thomas Henry Huxley
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Postby Lars » Wed Jun 13, 2007 6:10 am

I suppose its the old "is the cup half full or half empty" question. I like the completely full notion.
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Postby viper498 » Wed Jun 13, 2007 6:22 am

Finn,

Very scary notion by the way. I know that it has been the topic of quite a few threads. Can you imagine that all this time researchers have been looking at the disease from an "in the box" perspective? What a waste, and furthermore how fundementaly wrong! Science should be proven. Why would any scientist assume the cause of any disease. It is imperative they know what causes before they proceed with any more research. (I mean duh!). That is like building a house on quick sand.

Look at the product of assuming. The DMD's. Oooooooo Ahhhhhh, what a miraculous discovery. Good job ;-) How efficacious!

Sorry for all the sarcasm.

Brock
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Postby Lyon » Wed Jun 13, 2007 8:42 am

finn wrote:What if MS is found to be a neurodegenerative disease and demyelination really would be caused by axonal degeneration (as suggested by some researchers)? In that case halting demyelination and promoting remyelination would have an effect only on reverseable disability. Permanent disability caused by slow neurodegeneration would still progress.
Hi Finn,
Not trying to start an argument and admittedly my foundation is a clinical trial which is still in progress and can't really be considered "fact" but if what you mention stands any chance of being correct, what is to be made of the results found in the Tovaxin clinical trials?

In the entire history of MS research there is much that has been suspected but little or nothing which could be considered undeniable fact.

One thing that is fact and is as specific as could be, is that the Tovaxin process isolates and removes myelin reactive T cells. Nothing more, nothing less.

Considering the results they've been finding, I don't see how those results could do anything but prove that, at least in RRMS, removing the myelin reactive T cells from circulation has a profound effect on lesion formation and disability progression, at least out to the point that people have been treated so far....6 or 8 years??

I'm all for covering all bases and the existance of alternate viewpoints but if the results they are finding with Tovaxin continue to pan out, it seems that any thoughts of axon damage first would have been proven without merit.

Bob
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Postby robbie » Wed Jun 13, 2007 12:27 pm

Considering the results they've been finding, I don't see how those results could do anything but prove that, at least in RRMS, removing the myelin reactive T cells from circulation has a profound effect on lesion formation and disability progression

Bob could you just explain how mylein reactive t cells are different in people with RRMS as opposed to SPMS or PPMS. When you shift from one to the other do things change about how you are being attacked or is it just the frequency and severity that changes.
Had ms for over 19 years now.
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