Step towards understanding MS's variability

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Step towards understanding MS's variability

Postby TwistedHelix » Mon Oct 13, 2008 6:12 am

How often have we wondered why the course of MS varies so much from person to person, and why we respond so differently to various treatments? This new discovery might be a step towards understanding that:
Public release date: 13-Oct-2008
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Contact: Amy Maxmen
amaxmen@rockefeller.edu
212-327-8393
Rockefeller University Press
Response to immune protein determines pathology of multiple sclerosis

New research may help reveal why different parts of the brain can come under attack in patients with multiple sclerosis (MS). According to a new study in mice with an MS-like disease, the brain's response to a protein produced by invading T cells dictates whether it's the spinal cord or cerebellum that comes under fire. The study—from researchers at the University of Maryland School of Medicine in Baltimore and Washington University in St. Louis—will be published online on October 13th in the Journal of Experimental Medicine.

In most MS patients, the disease primarily affects the spinal cord and the white matter of the brain. But a small percentage of patients develop an atypical form of the disease, which primarily affects the cerebellum—the part of the brain that controls sensory perception and movement. For these patients, the disease tends to progress more rapidly and the prognosis is particularly bleak.

MS ensues when the body's T cells invade the brain and trigger nerve-damaging inflammation, in part by secreting proteins called cytokines. According to the new study, lead by Washington University scientist John Russell, the brain's response to one particular immune protein, called interferon-g (IFNg), determines which part of the brain the T cells attack. In mice that are oblivious to IFNg (because they lack its receptor), mice suffer cerebellum and brain stem inflammation, but their spinal cords are spared. When IFNg receptors were left intact, the reverse occurred.

Exactly how the brain's response to IFNg directs the T cell attack is not yet known, but the authors suspect that IFNg triggers a localized production of T cell-attracting proteins in the spinal cord. Translating the details of the "conversation" between T cells and brain cells, suggests Russell, might bring scientists closer to understanding the variable manifestations of human MS.
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Postby carolew » Mon Oct 13, 2008 6:56 am

very good find Dom... Carole
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Re: Steps towards understandin MS's variability

Postby NHE » Mon Oct 13, 2008 6:47 pm

Hi Dom,
Thanks for the interesting article. Do you know if the interferon-g that they discuss is the same as interferon-gamma or is it a newly discovered type of interferon?

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Re: Step towards understanding MS's variability

Postby HarryZ » Tue Oct 14, 2008 4:12 pm

Dom,

Interesting article but I have two concerns.

The first is the fact that their research is based on results from the poor MS mouse. EAE isn't anything like human MS and for decades, findings in this area have lead to huge amounts of disappointment for MS patients.

The second point is the reference that MS inflammation is "caused" by the patient's immune system, something that has not ever been proven. We know that this inflammation can exist in patients without the immune system being involved.

I sure wish they would make some huge discovery with this disease that didn't come from the MS mouse.

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Postby TwistedHelix » Wed Oct 15, 2008 7:01 am

I'm as confused as you are: I thought the symbol for gamma was a kind of handwritten letter "Y", but that comes from my days hunting moths, (don't ask, it's a long story),* so I'm not sure what the, "g" means. If it is interferon gamma, then that has been known for a long time to significantly worsen MS.
I agree that that poor old mouse is long overdue for retirement, and it's a scandal that EAE is still the only model we have, but for the moment we're stuck with either cells in a Petri dish or a disabled rodent and I haven't heard of any better models on the horizon. We can only hope that, whatever the differences, useful pointers could be found.
As for the reference to, "inflammation", etc., I get fed up with reading that as well. Whenever I see it I hope that it's simply down to a journalist searching for a quick, 3-line description of MS and lifting it from a 20 year old self-help leaflet.


*Perhaps "hunting" sounds a bit grand… you only need a teensy weensy rifle and mounting the antennae on a wooden plaque above the fireplace is, to be frank, not that impressive,
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