Remyelination

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Remyelination

Postby scoobyjude » Sun Dec 09, 2007 10:11 pm

Mice again I know but maybe it will lead to something... It is from the Mayo Clinic

December 09, '07: Antibody Repairs Myelin Sheath in Multiple Sclerosis
Category: M.S. Research Study Reports Posted by: stuart
Obtained from the Virtual Medical Ctr website


Antibody Repairs Myelin Sheath in Multiple Sclerosis


Abstract
Mayo Clinic researchers have found that a human antibody administered in a single low dose in laboratory mouse models can repair myelin, the insulating covering of nerves that when damaged can lead to multiple sclerosis and other disorders of the central nervous system.

9 Dec 2007

The study was presented on Oct. 9 at the American Neurological Association meeting in Washington, D.C.

"The repair of chronic spinal cord injury is seldom modelled in laboratory studies, but it is an important reality for the treatment of humans. The concept of using natural human antibodies to treat disease of this kind has not yet been tested in humans, but these research findings are very promising," says Moses Rodriguez, M.D., a Mayo Clinic neurologist and the study's corresponding author. "The findings could eventually lead to new treatments that could limit permanent disability," states Arthur Warrington, Ph.D., a Mayo Clinic scientist and study author.


Myelin repair normally occurs spontaneously, but in multiple sclerosis and other disorders of the central nervous system, the myelin repair process occurs very slowly or fails altogether. Researchers are trying to determine how to speed up the myelin healing process, which they hope will eventually lead to new treatments for patients.

The antibody, which was genetically engineered from a single cell, binds to myelin and the surface of cells in the brain and spinal cord, then it triggers the cells to begin the repair process called remyelination. This antibody is the first known reagent designed to induce repair by acting within the central nervous system at the damage sites on cells responsible for myelin synthesis.

The study uses laboratory mouse models of chronic progressive multiple sclerosis in humans. The severity of the disease and also success of the treatment were largely defined by how naturally active the mice were, particularly during the night because mice are nocturnal and are especially active at this time. They received a single dose of the antibody. A minimum of 25 mcg/kg was needed to trigger remyelination, which is equivalent to about 2 mg in the average adult, considered a very low dose. The myelin repair plateaued after five weeks in the mice models.

In addition, when combined with daily methylprednisolone, (an immune modulating steroid) the antibody still promotes remyelination in mouse models. This is an important fact because the first multiple sclerosis patients treated with the antibody will have been treated first with methylprednisolone.

As a naturally occurring protein of the immune system, antibodies do not appear to carry any side effects, nor are they toxic - even when administered at 4,000 times the minimal effective dose - though the concept has not yet been tested in humans, the researchers say.

In summary, this antibody:
* Promotes remyelination with a single dose as low as 25 mcg/kg in mice models
* The remyelination plateaus at five weeks after a single dose
* Converts a model of chronic immune mediated demyelination to one that repairs with the speed of a toxin induced model of demyelination

In terms of replicating the findings in humans, the researchers have already produced the antibody through genetic engineering and conducted preliminary toxicology experiments in mice showing that 1,000 times the therapeutic dose is not toxic. The study continues to be explored in animal models and eventually, in clinical trials.

In short, the critical finding is that when combined with methylprednisolone, the antibody still effectively promotes remyelination and does not make the mice worse, Dr. Warrington states.

The study was funded by the National Institutes of Health, the National Multiple Sclerosis Society, Multiple Sclerosis Society of Canada, the Hilton Foundation and Mr. and Mrs. Eugene Applebaum.


(Source: Meeting of the American Neurological Association, October 2007 : Amy Reyes : Mayo Clinic : December 2007)
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Postby TwistedHelix » Mon Dec 10, 2007 7:12 am

Scooby, this is really exciting research. I found the sentence about how the natural activity levels of the mice affected not only the severity of disease but also the effectiveness of drugs to be puzzling and intriguing: I wonder which way round it was? I mean, were the most active mice the worst affected, or vice versa? It's striking how many of us report being particularly active before the illness hit.
Apart from anything else, this link between disease and activity levels is a new one on me – maybe it'll provide a new avenue for research. I can't help thinking that, if you're susceptible to glutamate excitotoxicity, overstimulation by too much physical exercise could turn out to be detrimental,
Dom
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Postby Lyon » Mon Dec 10, 2007 7:47 am

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Postby scoobyjude » Mon Dec 10, 2007 11:51 am

Dom and Bob, I wasn't able to find any more info except the same press release. Maybe someone else can.

My understanding was that the myelin repair process in MS is so slow that it allows much more damage to occur from the attack than normal. Even if it was no longer under attack the repair process is very slow or non-existent. Isn't that why we have lasting damage? I was guessing that that is why speeding it up would improve recovery with little to no disability. Am I wrong? It seems that even after my attacks have stopped, complete recovery has still taken quite awhile if at all. I am not as scientifically knowledgable as either one of you so I welcome input.
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Postby Lyon » Mon Dec 10, 2007 3:07 pm

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Postby scoobyjude » Mon Dec 10, 2007 11:16 pm

There is no such thing as bad MS research, but I think it's obvious that better "cures" are closer to fruitation


I agree and I think remyelination is the most promising avenue that is being researched.
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Postby Lyon » Tue Dec 11, 2007 8:37 am

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Postby TwistedHelix » Wed Dec 12, 2007 7:57 am

In my opinion remyelination can only be a good thing because it should, at the very least, protect the axons from damage. There is even some experimental indication that electrophysiological function can be restored to some extent: I think if we can remyelinate faster than demyelination can occur we would have a useful stopgap which would buy us some time and stave off the worst of the damage, however , remyelinated areas are always prone to further demyelination, the new myelin is always much thinner than the old, the nodes of Ranvier are closer together, and the nodes themselves are larger, all of which mean that saltatory conduction is less efficient than it would otherwise be. I just wanted to point that out because it's easy to think, " MS is a loss of myelin, therefore simply getting the myelin back is the answer".
The speed of remyelination also varies between acute and chronic MS, which suggests to me there is something specific to the disease that interferes with this process either by inhibitory cytokines or reducing the number of oligodendrocytes and precursors, (which deplete when there are multiple episodes in the same lesion), or failure to recruit oligodendrocyte precursor cells.
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Postby gwa » Wed Dec 12, 2007 9:13 am

dom,

No more happy remyelination posts from you. I am going to go back to bed and cover my head.

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Postby Lyon » Wed Dec 12, 2007 9:45 am

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Postby TwistedHelix » Wed Dec 12, 2007 12:51 pm

Hi Bob,
I agree with you about promising therapies that are in the pipeline, but just in case they come to nothing, (which isn't exactly unheard of), it will be good to have another option to try which will protect our nerves from attack until such time as a complete halt to the disease process is available.
Contrary to what you might expect, acute demyelinating events with their rapid onset prompt a much quicker response than the long, slow chronic phase: to paraphrase Kesselring, "… it is not uncommon to find remyelination commencing within a few days of the onset of an event. In contrast, in cases of chronic MS, remyelination, if present at all, is generally restricted to inactive plaques and is absent in actively demyelinating lesions. There, remyelination appears to start much later in the course of the legion's evolution".

gwa, please come out from under there! I didn't mean to shoot the idea of remyelination down in flames! Maybe these researchers are talking about FULL remyelination, and even if not it's an important step forward and an amazing breakthrough anyway.
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