This Is MS Multiple Sclerosis Knowledge & Support Community

http://www.newsdaily.com/stories/tre57g4ke-us-ms-drug/

Would love to hear what my knowledgeable friends on this board think about this announcement. Drug that keeps blood vessels from contracting. Not as a new treatment per say--but seems this might fit into the CCSVI model.

CHICAGO, Aug. 17, 2009 (Reuters) — A widely used blood pressure drug may hold promise as a treatment for multiple sclerosis, U.S. researchers said on Monday.

Lab tests found the generic drug lisinopril, developed by Merck and sold as Prinivil or Tensopril, prevented paralysis in mice with a form of MS.

"Lisinopril was quite powerful, and could even reverse paralytic disease (in mice)," said Dr Lawrence Steinman of Stanford University School of Medicine in California, whose study appears in the Proceedings of the National Academy of Sciences.

Lisinopril, also sold by AstraZeneca as Zestril, is an angiotensin-converting enzyme, or ACE inhibitor. It acts by blocking angiotensin, a hormone that makes blood vessels contract, increasing blood pressure.

"The angiotensin system is critical for maintaining blood pressure, but it may play other roles," Steinman said in an e-mail. He said angiotensin is directly related to a biochemical mechanism called nuclear factor kappa B, or NF-kB, which underlies inflammation.

MS occurs when the immune system mistakenly attacks the myelin sheath protecting nerve cells, disrupting communication between the brain and other parts of the body. It affects about 2.5 million people globally, producing symptoms that range from mild illness to permanent disability.

Since both MS and high blood pressure are diseases caused in part by inflammation, Steinman and colleagues wanted to see if angiotensin was involved in the autoimmune disease.

Steinman's earlier work on inflammation in MS helped lay the groundwork for the blockbuster drug natalizumab or Tysabri, sold by Biogen Idec and Elan Corp.

For the latest research, Steinman's team studied brain tissue from patients with MS. They found elevated levels of receptors -- molecular doorways in cells -- for angiotensin. They also found more receptors for the enzyme that is blocked by the drug lisinopril.

"The receptors were on blood vessels but also on neurons and surrounding brain cells," Steinman said.

The researchers studied the effects of the drug using mice injected with a chemical that causes them to develop MS-like symptoms.

The team gave lisinopril to healthy mice, then gave the injection that triggers the MS-like disease. Mice that got lisinopril first did not develop MS.

Mice that had been injected with lisinopril had an abundance of immune system cells known as regulatory T cells that are capable of damping down the immune system.

When they transferred regulatory T cells from mice exposed to lisinopril into a paralyzed mouse, "they quickly reversed paralysis," Steinman said.

Steinman said the finding suggests the same effect might occur in people with MS, and possibly other autoimmune diseases.

"It will be important to test whether lisinopril and other angiotensin blockers can do this in MS patients," he said. "We are trying to secure funds to run such trials beginning next year."

I think this news report is related to this finding, at least the people involved. It all seems to be specifically related to the immune system.
stanford_researchers_find_protein_targets_for_potential_treatment_of_multiple/index.html

HOWEVER, where it does relate to CCSVI is that these guys are at the same University as Dr Dake. Maybe they should talk? (oh please.please.please.please...)
Especially since Dr May Han is coming down to Australia in October to speak at the "PROGRESS IN MS RESEARCH - MSRA Scientific Conference and Public Lecture"
http://www.msra.org.au/research/Progres ... erence.php

Interesting material that you might think has something to do with us, but this is helping in a way that does not correlate with CCSVI

The ace inhibitors are potent anti-inflammatory drugs. Angiotensin is pro inflammatory at the cellular level, so blocking it is anti inflammatory.

The Marshall protocol uses huge doses of this drug for anyone with an autoimmune disease. The dose they use of benicar is 4 times as high as normally used for blood pressure. I won't go into their theory, but the people who have done that feel it helped may have benefited from the anti inflammatory effects of the drug and not in the way the MP people say they did.

There is another person who has been suggesting for several years that ace inhibitors may be used for autoimmune diseases specifically for the potent anti inflammatory effects, but I can't find the reference cause my old computer died an untimely death and I lost all my favorite links....

But here is yet another idea along these lines
http://jpet.aspetjournals.org/cgi/content/full/307/1/17

It is not surprising that the ace inhibitors reduce EAE...anything that stops inflammation cures EAE.

This is more of what I think of as "off topic" research; people getting all excited about something that can't help in the end.

IS is evidence based? yes. They actually did give it to mice and it actually did help. But does that mean it will result in effective treatment? only to the extent that MS and EAE are the same...which we know they are not at all the same since EAE is curable even with simple things like copaxone.

I am sure that it will reduce inflammation in the same way any strong anti inflammatory drug or approach (ie hicy) does. I feel positive it has the potential to reduce enhancement on MRI lesions because enhancing lesions are lesions that are allowing inflammatory components to cross the BBB.

But I am equally certain, and this is mere opinion so take it as such, this is just as useless as all the other things that kill off inflammation but do not, in the end, help MS by altering the progression of disability.

How many ways can we knock out inflammation and then get all excited that the lesions are not enhancing then spend 8 years finding out it does not appreciably reduce actual disability before we finally get some people thinking 'Gee do the same thing get the same results..."?

Forgive the off topic rant but after 18 years of this kind of big announcement I am a little tired of the short sightedness that continues to get excited about this kind of "science" when in reality it ALWAYS starts from "how can I get rid of the inflammation here?" as if that has already proven to be the actual problem, when in reality that is still an assumption, no better than a guess.

If CCSVI is the cause of MS, inflammation is only a response to that injury--not the primary problem.

mrhodes40 wrote:But I am equally certain, and this is mere opinion so take it as such, this is just as useless as all the other things that kill off inflammation but do not, in the end, help MS by altering the progression of disability.

I have a lot of similar feelings based on the quote above. It was reaffirmed when my neuro and Dake had to play "where's Waldo" to find my lesions, and yet I still keep getting worse. So to many MS'ers, this could be something since knocking down inflammation can make them feel better. But to those of us lucky enough to keep progressing in the absence of enhancing lesions, well we have to keep looking elsewhere.

oo

Good point, good point, that was a grand assumption. I haven't noticed any progression yet (knocking on wood) so, so far so good!

Bob wrote:

Your mistake in this is in assuming that "absence of enhancing lesions" is synonymous with "absence of inflammation".

Hmm, I have a neuro who uses the terms synonymously. As the higher Tesla MRI's are used maybe we will see low grade inflammation when there are no enhancing lesions.

And, like Lew I have not noticed any progression.

Sharon

I'd like to weigh in here.

Mel has recently been tested by a 7.5T MRI machine and there was no signs of inflamation at all.

And no further or gray matter lesions were discovered.

Of course she was post hicy and pre surgery.

I was relieved I expected the 7T to pick up lots more damage.

more as an fyi than anything else.

As the higher Tesla MRI's are used maybe we will see low grade inflammation when there are no enhancing lesions

I agree. These new high tesla MRI's are really showing interesting material and I hope it means a much quicker resolution to the question does stenosis removal result in lesion changes.

oo

Bob,

I'll upload the 1.5T and 7.5T images to my site if you like?

Interesting comparison.

Jamie, where'd Mel get that, I'd like to see it! The research pictures I've seen (there is a link on the research sticky) are impressively clear.

I'll PM you the link once I've done it.

They put her through the 7T under an informal study, she's friends with some of the people there.

THANKS
Oh wow, do they want a bunch of new friends????

but, hey, maybe they'd see what Mel looks like now after stents??

mrhodes40 wrote:Interesting material that you might think has something to do with us, but this is helping in a way that does not correlate with CCSVI...

The ace inhibitors are potent anti-inflammatory drugs. Angiotensin is pro inflammatory at the cellular level, so blocking it is anti inflammatory.

Hi there,

I've been following the CCSVI story for a while now, both on the forums and outside of them, and I just wanted to weigh in on this. ACE inhibitors are not, strictly speaking, anti-inflammatory drugs. Their primary use is in treating high blood pressure. The rationale is that angiotensin (as its name implies) causes blood vessels to constrict, which causes blood pressure to be higher. By blocking the formation of angiotensin from its precursor, ACE-inhibitors counteract the effect of angiotensin, resulting in lower blood pressure.

Put that way, it kind of makes sense that ACE-inhibitors might relate to CCSVI. If the venous stenosis that Dr. Zamboni found is related to increased angiotensin activity (or increased number of receptors, or whatever), then it's logical that an ACE-inhibitor would help counteract the stenosis.

Keep up the good fight, folks!

Ed
(2nd year medical student)