FTY 720 (Fingolimod) Considered for Stroke (Ischemia)

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

FTY 720 (Fingolimod) Considered for Stroke (Ischemia)

Postby Shayk » Sun Nov 01, 2009 3:54 pm

Hi all

I posted some info about the development of FTY 720 (Fingolimod) for stroke in the drug pipeline but thought I'd post it here as well given the apparent reluctance of some neuro's to consider the impact of CCSVI in people with MS. (The link in that post is open access but you need to register) More info:

The immunomodulatory sphingosine 1-phosphate analog FTY720 reduces lesion size and improves neurological outcome in a mouse model of cerebral ischemia
Cerebral ischemia is accompanied by fulminant cellular and humoral inflammatory changes in the brain which contribute to lesion development after stroke.

A tight interplay between the brain and the peripheral immune system leads to a biphasic immune response to stroke consisting of an early activation of peripheral immune cells with massive production of proinflammatory cytokines followed by a systemic immunosuppression within days of cerebral ischemia

(Wonder if that could be "RRMS" in action--activation of peripheral immune cells and proinflammatory cytokines followed by "immunosuppression"?)
Recent work has documented the importance of T lymphocytes in the early exacerbation of ischemic injury.

We found that treatment with FTY720 (1mg/kg) reduced lesion size and improved neurological function after experimental stroke in mice,

Also interesting, at least to me, is this abstract that includes two authors who've done lots of research in MS--H. Offner and AA Vandenbark. If it's been posted before, I missed it.

Effect of experimental stroke on peripheral immunity
The profound damage to the CNS caused by ischemic lesions has been well documented. Yet, relatively little is known about the contribution to and effects on the immune system during stroke.

These novel findings advocate the need to develop or effectively utilize agents that can block early neural splenic activation and modulate immune cells specific for brain antigens as a means to prevent mobilization of T and B cells carrying a cytokine death warrant to the brain.


So, it at least seems to me that the immune response to stroke (ischemia) bears a striking resemblance to the immune response in people with MS--I mean really, T cells, B cells, and an MS drug in the pipeline, FTY 720 (Fingolimod) proposed to treat stroke.

Now, what exactly is it that the neuro's dismiss with CCSVI? Do they think CCSVI either can't or doesn't result in ischemia in people with MS? I truly don't get it.

Take care all--end of rant.

Sharon
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Postby cheerleader » Sun Nov 01, 2009 4:37 pm

Thank you for these links, Sharon. Once again, fantastic research. I had posted an article regarding research into IL-23 antibodies in the general thread-

HONG KONG, Aug 3 (Reuters) - Scientists have identified a class of immune cells that floods the brain soon after a stroke, causing inflammation and more neurological damage.

In their experiment, Yoshimura and his colleagues induced a stroke in several groups of mice and observed how the subsequent flood of immune cells caused inflammation and more damage.

One of the first groups of immune cells to enter the brain is called interleukin-23 (IL-23).

"IL-23 itself is not harmful, but it activates other immune cells like T-cells and macrophages and these attack the brain. This same sort of activation occurs when the body is invaded by microbes and during any sort of injury," Yoshimura said.

The mice that suffered the least brain damage were those genetically engineered to be deficient in IL-23.

"IL-23 operates immediately after stroke or one day later ... so the sooner the intervention (blocking of IL-23) happens, the more protective it is for the brain," he said.

The experts hope to apply the findings of the study, published in Nature Medicine, on people.

He added that an experimental antibody against interleukin-23 is currently in phase 2 clinical trial.

"It is to be used for inflammatory diseases, like inflammatory bowel disease. So if it is approved, we can try this drug on stroke patients," he added.

http://www.reuters.com/article/latestCrisis/idUST264188

I have no idea why the connection between ischemic injury in stroke and MS is being ignored. It is frustrating to me, and you can rant all you want. I do know that Dr. Dake is now testing oxygenation levels in the brain prior to and after stenting, and will be writing about this. Chronic low level hypoxia/ischemic injury looks exactly like MS injury- from gray matter injury leading to white matter lesions (which are known to be secondary.)

In chronic venous stasis in the legs- it is well-recognized medical fact that hypoxic injury creates the ulcers and lesions and activates the immune system. CCSVI is venous stasis in the brain! Which is really hypoxic assault.

We're laypeople....this is not rocket science. Any doctors want to come out of the woodwork and explain this to us???
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby ozarkcanoer » Sun Nov 01, 2009 4:52 pm

Thanks, cheer.... I sent the link to this article to my "brain friend", Dr. Woolsey... I'll see him Wednesday !!!! :D :D
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Postby radeck » Sun Nov 01, 2009 5:28 pm

Awesome thread!!

Just a few days ago Marie made us aware of work showing similar effect of Minocycline, a tetracycline antibiotic (http://www.thisisms.com/ftopict-8558.html).

The Telegraph story she referenced is here:

<shortened url>

And the research article is this:

<shortened url>
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Postby mrhodes40 » Sun Nov 01, 2009 7:50 pm

Sharon=wow 8O :D :D :D

What an incredible resource you are-- thank you for posting this insightful idea!

It is good there is so much peripheral information that can be tied in to the original work, such as this ischemia material. It does strengthen the CCSVI paradigm to recognize there is some material in the body of literature already that suggests that this may be a good explanation for MS damage. Seeing that fingolomod helps stroke in a way that is similar to the CCSVI model is very interesting!

Thanks for reposting the links to the minocycline work Rad.
I'm not offering medical advice, I am just a patient too! Talk to your doctor about what is best for you...
http://www.thisisms.com/ftopic-7318-0.html This is my regimen thread
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