lisinopril

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lisinopril

Postby dignan » Mon Aug 17, 2009 7:28 pm

Interesting potential treatment...


Inexpensive hypertension drug could be multiple sclerosis treatment

August 17, 2009 - Turning serendipity into science, researchers at the Stanford University School of Medicine have found a link, in mice and in human brain tissue, between high blood pressure and multiple sclerosis. Their findings suggest that a safe, inexpensive drug already in wide use for high blood pressure may have therapeutic value in multiple sclerosis, as well.

While neurology professor Lawrence Steinman, MD, senior author of the new study, cautioned that extensive clinical trial work is needed to determine if the drug, known as lisinopril, can do in humans what it does in mice, he is excited that "we were able to show that all the targets for lisinopril are there and ready for therapeutic manipulation in the multiple-sclerosis lesions of human patients. Without that, this would be just another intriguing paper about what's possible in the mouse."

The paper will be published online Aug. 17 by the Proceedings of the National Academy of Sciences.

for the full article:
http://www.physorg.com/news169744882.html
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Postby euphoniaa » Thu Aug 20, 2009 4:23 am

Hi dignan,

I decided this morning that maybe it was time to post a single thread with the title "Lisinopril" and add links to all the other TIMS threads that have been discussing it. I did a search, and it was already right here. Thanks.

Sorry I missed yours, which was the first one, after all, but my medphobia (Lisinopril is one of the reasons) generally keeps me out of the Drug Pipeline forum altogether. :)

So, here are links to the other discussions on the same research as this one.

From the General forum:
http://www.thisisms.com/ftopict-7919.html

From the CCSVI forum:
http://www.thisisms.com/ftopict-7902.html

And the thread in which I posted about my experience with my usual tiresome verbosity :) :
http://www.thisisms.com/ftopict-7900.html


Edited to add a link to another thread:
http://www.thisisms.com/ftopict-7936.html

Edited again to add a link to another thread:
http://www.thisisms.com/ftopict-7947.html

Edited again to add another thread from CCSVI forum:
http://www.thisisms.com/ftopict-8058.html
Last edited by euphoniaa on Tue Sep 08, 2009 4:10 am, edited 3 times in total.
Dx'd with MS & HNPP (hereditary peripheral neuropathy) 7/03 but must have had MS for 30 yrs before that. I've never taken meds for MS except 1 yr experiment on LDN. (I found diet, exercise, sleep, humor, music help me the most.)
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Postby dignan » Thu Aug 20, 2009 10:19 am

euphoniaa, thanks for collecting all the links. The multiple threads thing happens a lot at TIMS, but it's not a bad thing. Better to get the information out in a lot of different places than not at all.
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Postby dignan » Sat Aug 29, 2009 9:18 am

Here is the Pubmed abstract of the study:


Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity

Proc Natl Acad Sci U S A. 2009 Aug 19.
Platten M, Youssef S, Hur EM, Ho PP, Han MH, Lanz TV, Phillips LK, Goldstein MJ, Bhat R, Raine CS, Sobel RA, Steinman L.
Departments of Neurology and Neurological Sciences and Pathology (Neuropathology), Beckman Center for Molecular Medicine Stanford University, Stanford, CA 94305.

The renin-angiotensin-aldosterone system (RAAS) is a major regulator of blood pressure. The octapeptide angiotensin II (AII) is proteolytically processed from the decapeptide AI by angiotensin-converting enzyme (ACE), and then acts via angiotensin type 1 and type 2 receptors (AT1R and AT2R).

Inhibitors of ACE and antagonists of the AT1R are used in the treatment of hypertension, myocardial infarction, and stroke. We now show that the RAAS also plays a major role in autoimmunity, exemplified by multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE).

Using proteomics, we observed that RAAS is up-regulated in brain lesions of MS. AT1R was induced in myelin-specific CD4(+) T cells and monocytes during autoimmune neuroinflammation. Blocking AII production with ACE inhibitors or inhibiting AII signaling with AT1R blockers suppressed autoreactive TH1 and TH17 cells and promoted antigen-specific CD4+FoxP3+ regulatory T cells (Treg cells) with inhibition of the canonical NF-kappaB1 transcription factor complex and activation of the alternative NF-kappaB2 pathway. Treatment with ACE inhibitors induces abundant CD4+FoxP3+ T cells with sufficient potency to reverse paralytic EAE.

Modulation of the RAAS with inexpensive, safe pharmaceuticals used by millions worldwide is an attractive therapeutic strategy for application to human autoimmune diseases.

http://www.ncbi.nlm.nih.gov/pubmed/19706421
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Postby euphoniaa » Tue Sep 08, 2009 4:54 am

I've been following the numerous lisinopril threads, since I have HBP and also had an extremely adverse experience with it. FYI - I've linked as many lisinopril threads as I've come across into my original post here (see above). :) I do feel obligated to point out a couple of things I've posted elsewhere also.

1. When they list a "dry cough" in the side effect profile, that's a major understatement. I found it more stressful and disabling than most anything MS has thrown at me. I disrupted many a meeting and lecture at work with my sudden coughing fits (sputter, gag, gasp, cough till you puke) and a good night's sleep was impossible. I assumed I had contracted some horrible bronchial illness that extended through a whole winter until someone mentioned The Lisinopril Cough (not my doc - she just added cough & sinus meds). Instead I dropped lisinopril and I was miraculously cured! You can Google the "ACE cough" or the "lisinopril cough" and find out more about it.

2. And before everyone runs out to ask for the "... inexpensive, safe pharmaceuticals used by millions worldwide..." they might want to consider the possibility that it may be contraindicated in your particular medical case and screwing around with your BP may be dangerous for you.

Although the treatment of high blood pressure has generally been a hit/miss/tryanotherdrug/miss/tryanotherdrug thing in the past (kinda like treating MS), now there's a machine that can tell them quickly where your problem lies and choose the best med for it - the Bio-Z machine. For example, it told them that the beta blocker I'd been taking was doing its job in that area and that my fluids were fine and I don't need to add a diuretic. It also said that I DO need to add something like an ACE inhibitor, but the side effects have prevented me from taking one.
**********

I do hope that this discovery leads to even more discoveries and MS knowledge (haha - like there IS such a thing) and I hope it turns out to be an option for others.

P.S. Unlike MS meds, at least with BP meds they can tell easily if they "work." :)
Dx'd with MS & HNPP (hereditary peripheral neuropathy) 7/03 but must have had MS for 30 yrs before that. I've never taken meds for MS except 1 yr experiment on LDN. (I found diet, exercise, sleep, humor, music help me the most.)
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Possible Alternative to Lisinopril ...

Postby ghmitch » Sun Sep 20, 2009 8:55 am

I took Lisinopril for years without any side effects at all. Only recently I started to have some problems with it and switched to another BP medication. That is when I began to have neuropathic problems in my left leg, then both legs, then up into my upper body. Now, 18 months after symptoms started, full body MRI shows abnormalities in my brain that results in a tentative diagnosis of MS. I am seeing the neurologist tomorrow and am going to request treatment with LDN. According to our local compounding pharmacist the local neurological group does prescribe LDN, so I hope to convince them to allow me to try it. I am also on a track to go back to the Lisinopril in spite of the side effects. They were nothing in comparison to what I am putting up with now and the dose of Lisinopril I would be taking now would be much lower than what I was taking before since my baseline blood pressure is so much better due to diet and lifestyle changes. While I am hoping I can tolerate the Lisinopril. IF it is significantly helpful, but the side effects are a problem, I will likely request to try Aliskiren. This one is very expensive, but not nearly as expensive as many MS drugs. Pharmacologically, it would seem likely to be just as beneficial as Lisinopril since it blocks the RAAS at its source. It might be an option for those who can't tolerate Lisinopril. Due to the timing of my encounter with MS, I really do suspect that Angiotensin Converting Enzyme played a role in triggering it. - George
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Postby LR1234 » Sun Sep 20, 2009 9:16 am

Thanks for the info George.
Do you think you had MS then all these years and the linisprol was preventing it from surfacing? You might also want to check your antiphospholipids and blood stickiness to make sure you don't have this problem as it mimics MS.
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Postby ghmitch » Sun Sep 20, 2009 5:07 pm

lr, My suspicion which is pure speculation is that I depleted my vitamin D levels to nothing by using all sorts of anti-inflammatories in an effort to deal with another autoimmune problem. During that time I started getting fungal infections in my mouth which only got resolved when I upped my Vitamin D supplementation to 1000IU/day. Then I switched from Lisinopril, which lowers ACE, to Cozaar, which likely increases it since it is an endpoint receptor blocker. So I suspect a deficiency in vitamin D which is anti-inflammatory, and an excess of inflammatory Angiotensin Converting Enzyme had a lot to do with causing my problem. I have now gotten my serum vitamin D levels in order and am now taking 7000IU of vitamin D3 per day to maintain them. Given what was revealed in the MRI, I am fairly confident that I am dealing with MS at this point. I don't have any clotting issues at all that would point to an antiphospholipid issue and all my blood work is grossly normal except for some T-Cell anomalies that would, if anything, seem to validate an autoimmune issue.

Ah, I just found something interesting. According to this paper: http://circ.ahajournals.org/cgi/content/full/circulationaha%3B111/3/315

We also found that losartan increased plasma ACE levels, similar to the effects of ACE inhibition and consistent with tonic negative feedback regulation of ACE by Ang II.


This would mean that while Lisinopril is inhibiting ACE while raising it, Losartan also raises ACE but DOES NOT inhibit it. This certainly seems like it could subject ACE receptors in the brain to a sudden inflammatory load from sudden removal of ACE inhibition accompanied by already artificially elevated levels of ACE. This might be something interesting. - George
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Postby ewizabeth » Sat Oct 10, 2009 11:59 am

I brought this up with my MS neuro and he gave me reasons why it wouldn't work. It was over my head so I can't tell you what the reasons were. I told him that I'd been taking Lisinopril for awhile and that it worked better for me than any of the other BP meds I'd been on and he didn't change his opinion.

Anyway, it's cheap so if it would work for someone, it seems like it would be fairly cheap to try it out as long as you didn't already have low blood pressure.
Take care, Ewizabeth Previously Avonex, Rebif & Copaxone RRMS ~Tysabri, 31 infusions, ended 9/09. Starting Copaxone 12/09, waiting for Cladribine to be approved in 2010.
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Postby LR1234 » Sat Oct 10, 2009 3:20 pm

Hi George, Sorry it has taken me this long to reply..for some reason it didn't show me you had responded.

I am not that familiar with the role of Ace inhibitors..its something I might read up on.

What other autoimmune disease do you have? (If you don't mind me asking)



L
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Postby jr5646 » Fri Dec 04, 2009 6:39 pm

For some strange reason, I believe this is the guy who got the ball rolling with monoclonial antibodies??? I'm almost certain he was trying to warn folks about the dangers of them though??? I'm looking for the connection, but can't find it at the moment.. Damm this brain fog... Maybe I'm wrong, but I think he was pissed for some reason and then formed bayhill..

http://www.bayhilltherapeutics.com/founders.html


Too bad he dosen't hook up with Dr. Dake (also at Stanford) to collaborate on the the ccsvi clinical trial....

Does anybody remember this or am loosing it???

OK how about pairing Lisinopril with ccsvi treatment?
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Postby japentz » Wed Jan 13, 2010 11:21 am

I started a thread in the CCSVI forum about Lisinopril (and Quinopril) which are Ace Inhibitors. I do not want to dwell on Lisinopril or any other Ace Inhibitor, the cough is MISERABLE and unliveable. Importantly, I wanted to talk instead about my trying and Angiotensin Receptor Blocker (ARB) in conjunction with MS. I am simple minded (more so due to the MS i have). ARBs perform a similiar function as the Ace Inhibitors but do so at a different place so they do not cause the cough.

DISCLAIMER: I took this experiment upon myself NO one at Stanford is performing a research study on me, nor would they do ANYTHING without real clinical trials on humans. Also I AM under a very good physicians care for my blood pressure and he would not let me try anything that would hurt me.

NOTE: I do not condone the use of Ace Inhibitors due to possible bad coughing side effects. I AM interested in hearing from people who also have high blood pressure and any effects that ace inhibitor or Angiotensin Receptor Blockers (ARBs) might have on their MS if they take them

********************

Hello all,

I am new here. I am glad to finally find an intelligent, thoughtful and informative MS community. I was trying to start a Journal on this (so far its not working.)

I live in Baltimore Maryland (well north of it). I was diagnosed with Relapsing Remitting MS in July of 2008. I am 46 years old. I had been exhibiting symptoms for about 2 or 3 years prior.

I had read an article by Bruce Goldman, a journalist for the Stanford School of Medicine regarding Dr. Lawrence Steinman's research which involved giving mice with and MS like disease, the ace inhibitor Lisinopril. Ace Inhibitors (as you may know) are medication for high blood pressure. The mice walked again.

I do have high blood pressure, and a rapid pulse. I was prescribed Avonex, which quite bluntly, is from hell. I felt terrible and it was not helping. In fear of PML, I did not wish to use Tsabri. I am currently using Copaxone (which at least does not make me feel sick, but does not really help either, that I can tell).

Based on this article I asked my regular doctor, internal medicine specialist, if I could try Lisinopril. (My neurologist was very negative on it, and got mad when I asked about current research. I felt he really is not up on MS research at all.)

I started Lisinopril, and within two days my 'ataxia' almost went away. I could curl the toes in my right foot and bend my ankle up again.

I contacted Bruce Goldman regarding my experience and he put me in touch with the research department. Bear with me . .this has to do with CCSVI.

This is the article published by Bruce Goldman:
http://www.eurekalert.org/pub_releases/2009-08/sumc-ihd081209.php

I wrote to them and they were very interested in what I was doing. Unfortunately, ace inhibitors such as Lisinopril, have a bad side effect of a HORRIBLE dry cough for a lot of people. I was one of them. I had to go off of it.

Researchers at Stanford were kind enough to work with me in communicating with Dr. Kimmel (internal medicine). I was sent their research paper on this along with some basic information. I did not understand this paper. I presented the correspondence and this research paper to Dr. Kimmel.

Honestly, I did not know that ace inhibitors worked by somehow relaxing the veins to allow more blood through, making them more pliable i guess. I did not understand the research paper. I just knew it made a mouse walk. I have MS . .I will try anything MS stinks!!

When I came across the Canadian Documentary on Dr. Paolo Zamboni I was amazed and very happy. Something FINALLY clicked as to why the myelin was being destroyed.

I created a web page for Dr. Kimmel with the video and the thread stickied at the top of the CCSVI forum where people were posting what was going on with treatment for CCSVI. I also sent him a hard copy of Zamboni's paper, Dr. Steinman's paper and the thread regarding those who have been treated for CCSVI here (stickied at the forum)

http://www.reallynews.com/zamboni

I then made an appointment with Dr. Kimmel to discuss all of this. He was at first skeptical. But observing the movement of my toes and ankle, he kept an open mind. I think he was very interested in this (especially with concern at my rapid pulse, that there was not another reason for).

We tried another ace inhibitor (Quinopril) with same WRETCHED consistent cough. Again, I got my balance back. But had to stop taking that medicine.

Then per the information provided and suggestion of Dr. Steinman, there was another blood pressure medicine called an Angiotensin Receptor Blocker (ARB) which did the same sort of function on veins but did not cause the cough.

SO I am trying this right now. Guess what? My balance again has somewhat improved. (I am on day 4 of medicine, and it starts to really do its thing in about 10 days).

So I believe Stanford’s researchers are on another angle to this and a medication treatment as opposed to surgery. Some of them are very skeptical about jumping into surgery for this and advised one person died from the procedure and another had to have an open heart operation due to the stent moving to the heart.

I am very lucky and honored to be in this dialog with Stanford. I am hopeful it will eventually lead to other things besides surgery that can be an effective treatment for CCSVI.

So I believe that 'opening up' veins may help. I am interested in hearing others experiences.

(I know ace inhibitors such as Lisinopril or Quinopril may cause bad and harsh coughing. it does for a lot of people (like me). What about ARBS such as Candesartan (which does not cause the cough). Any experiences to share?

Thanks!
Judy
RRMS, Diagnosed July 2008
Baltimore, MD USA
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Postby SaintLouis » Wed Jan 13, 2010 2:06 pm

Would Diovan fall into that same category?
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Lisinopril from some users of the drug

Postby AndrewKFletcher » Thu Jan 14, 2010 3:09 am

Find us on Facebook.com/InclinedBedTherapy
IBT website: http://inclinedbedtherapy.com
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Postby Frank » Fri Jan 15, 2010 5:05 am

Somewhat off-topic, but this current report shows that ARBs and ACEs might have significant impact on the occurance and course of Alzheimers dissease:
http://www.sciencedaily.com/releases/20 ... 201345.htm

--Frank
Treatment: Gilenya since 01/2011, CCSVI both IJV ballooned 09/2010, Tysabri stopped after 24 Infusions and positive JCV antibody test, after LDN, ABX Wheldon Regime for 1 year.
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