phase 1 trial of hypertension drug

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phase 1 trial of hypertension drug

Postby Cece » Tue Jan 28, 2014 6:05 pm

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Re: phase 1 trial of hypertension drug

Postby cheerleader » Tue Jan 28, 2014 7:14 pm

It's interesting news. The NIH is moving forward with Lisinopril..which costs pennies right now, and will probably cost pwMS thousands with it's NEW, improved name.
Here's more on the new MS meds which target blood flow, not the immune system--including Lisinopril.
Pharma and MS researchers have figured out how to move forward....piggy backing on Dr. Zamboni's research,

With the growth of research into the connection of MS to cerebral blood flow, we've seen an interest in exploring new ways to address hypoperfusion (slowed blood flow), endothelial dysfunction (damaged blood vessels) and brain atrophy (loss of brain tissue).

Why is this? Because MS specialists, neurologists and advocacy groups are much more comfortable designing, testing and recommending a drug for MS, rather than encouraging healthy lifestyles and treating venous malformations. You cannot monetize or patent a diet, exercise and angioplasty. It's impossible to have a placebo-controlled clinical trial for lifestyle. But you can develop a drug and make a lot of money selling it to a population with a chronic and degenerative disease.


http://ccsviinms.blogspot.com/2013/08/m ... blood.html
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Re: phase 1 trial of hypertension drug

Postby NHE » Wed Jan 29, 2014 12:23 am

Steinman's 1999 paper with lisinopril in EAE used a dosage of 10 mg/kg/day. This is a dosage that's roughly 60 times higher than the standard prescription for high blood pressure. I hope it helps, but I wonder about the clinical relevance of such a high dosage.

http://www.ncbi.nlm.nih.gov/pmc/article ... q14948.pdf
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Re: phase 1 trial of hypertension drug

Postby cheerleader » Wed Jan 29, 2014 9:02 am

NHE wrote:Steinman's 1999 paper with lisinopril in EAE used a dosage of 10 mg/kg/day.
http://www.ncbi.nlm.nih.gov/pmc/article ... q14948.pdf

Yowza! 10mg for a little mouse w/EAE! Here's dosage info for hypertension.
Initial dose: 10 mg orally once a day, in patients not receiving a diuretic.
Maintenance dose: 20 to 40 mg orally once a day.
Some patients appear to have a further response to 80 mg, but experience with this dose is limited.


Since I wrote about this topic on FB, I've had several posters come on and say they've already tried Lisinopril, or are on it, and it hasn't helped their MS much. One person even developed the Lisinopril cough, and stopped taking it. This side effect happens in a third of the people on ACE inhibitors...I can only imagine a higher dosage would provoke more side effects.
In this case, the insoluble by-products of the drugs, called kinins, are not filtered out of the blood. They then flow out of the kidneys and lodge themselves in the lungs' bronchial tubes. The coughing spells represent the body's attempt to expel the kinins from the lungs. Even after the drug is stopped, the cough can linger for months until all the kinins eventually find their way out of the lungs.
http://www.aarp.org/health/drugs-supple ... itors.html

There are other ways to improve endothelial dysfunction and reduce inflammation, but pharma can't sell you vegetables, sunshine and track shoes.
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Re: phase 1 trial of hypertension drug

Postby erinc14 » Wed Jan 29, 2014 10:36 am

what is the difference between a bp medicine and aspirin ?
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Re: phase 1 trial of hypertension drug

Postby cheerleader » Wed Jan 29, 2014 3:48 pm

erinc14 wrote:what is the difference between a bp medicine and aspirin ?

Lisinopril works on the endothelium and blood vessels.
Here's more on the method of action in Lisinopril--it is an ACE inhibitor, and modulates angiotensin, which is a hormone that causes vasoconstriction.
Angiotensin immediately causes blood vessels to constrict. “That raises your blood pressure so when you stand up to get out of a chair, you don’t fall down and faint,” said Steinman, who is also the George A. Zimmerman Professor in the medical school. But angiotensin overactivity causes chronic hypertension. Lisinopril controls blood pressure by blocking an enzyme that converts angiotensin’s precursor into the active hormone. The drug also appears to have certain anti-inflammatory properties.
http://med.stanford.edu/ism/2009/august/lisinopril.html

Aspirin works on the blood itself. It is an anti-platetet, or blood thinner. And it is an anti-prostaglandin, or anti-inflammatory.

I wrote up a review of the new slew of MS drugs which address the blood and endothelium---rather than the immune system.
http://ccsviinms.blogspot.com/2013/08/m ... blood.html

cheer
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Re: phase 1 trial of hypertension drug

Postby Cece » Wed Jan 29, 2014 4:22 pm

cheerleader wrote:Since I wrote about this topic on FB, I've had several posters come on and say they've already tried Lisinopril, or are on it, and it hasn't helped their MS much.

Lisinopril would be prescribed to people with specific problems, so those problems might have gotten in the way of any benefit of lisinopril on the MS. A controlled study is a good idea, but it's not likely to be a miracle drug. I wish we could see studies of drugs on patients AFTER they've had CCSVI treatment.

I need Dr. Tucker to stop on by and explain how hypertensive drugs would impact in the mathematical model with focal points of hypertension caused by CCSVI blockages! If blood pressure was lowered overall, then in the combining waves (outbound and reflux), the pressure would be lower and the disruption of the BBB would be less?
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Re: phase 1 trial of hypertension drug

Postby NHE » Wed Jan 29, 2014 6:05 pm

cheerleader wrote:
NHE wrote:Steinman's 1999 paper with lisinopril in EAE used a dosage of 10 mg/kg/day.
http://www.ncbi.nlm.nih.gov/pmc/article ... q14948.pdf

Yowza! 10mg for a little mouse w/EAE!

That 10 mg dosage was per kg. A mouse wouldn't get the full 10 mg unless it weighed 2.205 lb. That's a big mouse! Image It's still ~60x higher than the typical dosage for a person though.
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Re: phase 1 trial of hypertension drug

Postby cheerleader » Wed Jan 29, 2014 6:06 pm

Hey Cece--
All of the research on lisinopril has been in mice with EAE, and the rationale for testing in humans with MS is this---

Angiotensin converting enzyme (ACE) and angiotensin receptors are up-regulated in MS lesions in the brain, which suggests a potential link between the angiotensin system and the disease. Lisinopril doses that are equivalent to those prescribed for humans with high blood pressure prevented the development of the paralysis that is characteristic of disease progression in EAE mice and reversed existing paralysis as well.


Why would ACE be upregulated in lesions in the MS brain? Maybe venous hypertension? Maybe ischemic-reperfusion injury? both of these situations see the same presentation of ACE upregulation. It's another connection to the vasculature. It doesn't have to point to venous blockages, per se--but it sure makes sense in the CCSVI paradigm.
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Re: phase 1 trial of hypertension drug

Postby 1eye » Wed Jan 29, 2014 7:54 pm

If there is any physiological difference between a mouse and a human, it might mean Dr. Tucker would have to change his model's assumptions.
"Try - Just A Little Bit Harder" - Janis Joplin
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Re: phase 1 trial of hypertension drug

Postby erinc14 » Thu Jan 30, 2014 8:49 am

thanks
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Re: phase 1 trial of hypertension drug

Postby erinc14 » Sat Feb 01, 2014 10:19 am

is there any way to find out what the drug is ?
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Re: phase 1 trial of hypertension drug

Postby cheerleader » Sun Feb 02, 2014 2:30 pm

Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Re: phase 1 trial of hypertension drug

Postby erinc14 » Mon Feb 03, 2014 8:14 am

cheerleader wrote:it's Lisinopril, erin
http://med.stanford.edu/ism/2009/august/lisinopril.html



great , thanks .
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