61 replies to this topic

[Turnbuckle]

Many of the drugs known to be useful in clearing plaques--including AZ plaques--have sulfonic acid end groups. Trodusquemine does, and so does the buffer HEPPS (aka EPPS), which is claimed to "wash away" beta amyloid in a mouse model of AZ. And also taurine (a dirt cheap bile acid), which does the same though not as efficiently.

 

For taurine--

 

We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages.

https://www.ncbi.nlm...pubmed/25502280

 

 

Studies conducted in laboratory animal models using both genetic and dietary models of hyperlipidemia have demonstrated that taurine supplementation retards the initiation and progression of atherosclerosis.

https://www.ncbi.nlm...pubmed/23224908

 

 

Another bile acid containing a sulfonic acid end group is TUCDA (a taurine conjugate of ursodeoxycholic acid)--

 

We have previously reported the therapeutic efficacy of TUDCA treatment before amyloid plaque deposition in APP/PS1 double-transgenic mice. In the present study, we evaluated the protective effects of TUDCA when administrated after the onset of amyloid pathology. APP/PS1 transgenic mice with 7 months of age were injected intraperitoneally with TUDCA (500 mg/kg) every 3 days for 3 months. TUDCA treatment significantly attenuated Aβ deposition in the brain, with a concomitant decrease in Aβ₁₋₄₀ and Aβ₁₋₄₂ levels. The amyloidogenic processing of amyloid precursor protein was also reduced, indicating that TUDCA interferes with Aβ production. 

https://www.ncbi.nlm...pubmed/25443293

 

 

And finally--

 

Targeted metabolomic profiling finds bile acid disturbances in Alzheimer’s disease.

 

Introduction Bile acids play complex roles in cell signalling and immunomodulation and they have been linked to Alzheimer’s disease (AD). This study used LC-MS/MS to comprehensively profile 22 bile acids in brain and plasma from AD patients and APP/PS1 mice. Materials and methods Metabolites in plasma and brain extracts were quantified by an established mass spectral method using the Biocrates Bile Acids kit. Lyophilized and powderised brain tissues (25± 0.5mg) were extracted in ethanol:PBS (300µl; 85%:15%) prior to analysis. Results In human plasma we detected significantly lower cholic acid (CA; 156±74 vs. 947±483µM; n=10) in AD patients than age-matched control subjects. Contrastingly, taurocholic acid was significantly higher (TCA; 87±25 vs. 39±12µM). In APP/PS1 mouse plasma we detected higher CA (10510±4498 vs1811±368µM; 6 months; n=5) and lower hyodeoxycholic acid (1009±226 vs. 364±192µM; 12 months) than WT. In human brain with AD pathology (Braak stages V-VI) TCA (19±6 vs. 4±2µM; n=10) and taurochenodesoxycholic acid (34±10 vs. 13±4 µM) were significantly higher than age-matched control subjects. In APP/PS1 mice we detected higher brain lithocholic acid (6±2 vs. 13±3µM; 6 months) and higher tauromuricholic acid (TMCA; 43±7 vs. 23±8µM; 6 months). TMCA was also elevated in 12 month old APP/PS1 mice (76±21 vs. 12±4 µM) along with 5 others: CA (83±22 vs. 25±7µM), deoxycholic acid (31±5 vs. 24±5µM), β-muricholic acid (73±17 vs. 25±10µM), Ω-muricholic acid (25±6 vs. 8±3µM) and TCA (48±20 vs. 11±7µM). Conclusions We present evidence that bile acid concentrations are disturbed in AD-pathology and further investigation of these changes is clearly warranted. 

 

https://www.research...eimer's_disease

 

 

 

Edited by Turnbuckle, 14 December 2017 - 02:11 PM.

[Rocket]

I would be in for a group buy.

[Rocket]

Bump.

Would love a group buy effort.

[StanG]

I'm interested also

[Daniel Cooper]

 

Many of the drugs known to be useful in clearing plaques--including AZ plaques--have sulfonic acid end groups. Trodusquemine does, and so does the buffer HEPPS (aka EPPS), which is claimed to "wash away" beta amyloid in a mouse model of AZ. And also taurine (a dirt cheap bile acid), which does the same though not as efficiently.

 

 

Are arterial plaques really similar enough to amyloid plaques that we can have any confidence that we can clear arterial plaques with these compounds (aside from trodusquemine)?

 

If you were going to pick one of those you listed to clear arterial plaque, which one would it be?  Taurine has the advantage of being cheap and well tolerated, but perhaps less effective.  What would be your pick?

[Daniel Cooper]

If you had some Trodusquemine, how would you administer it?  In the animal studies they administered it intraperitoneally, which would probably not be my route of choice.

 

Can we get enough in subq?

 

 

 

[Turnbuckle]

 

 

Many of the drugs known to be useful in clearing plaques--including AZ plaques--have sulfonic acid end groups. Trodusquemine does, and so does the buffer HEPPS (aka EPPS), which is claimed to "wash away" beta amyloid in a mouse model of AZ. And also taurine (a dirt cheap bile acid), which does the same though not as efficiently.

 

 

Are arterial plaques really similar enough to amyloid plaques that we can have any confidence that we can clear arterial plaques with these compounds (aside from trodusquemine)?

 

If you were going to pick one of those you listed to clear arterial plaque, which one would it be?  Taurine has the advantage of being cheap and well tolerated, but perhaps less effective.  What would be your pick?

 

 

Taurine is a good place to start. As you say, it's dirt cheap, easily available, and safe. And for the first two reasons most researchers are not going to be interested in it. But there are some--

 

Role of taurine in the vasculature: an overview of experimental and human studies

 

Oral taurine in hypertensive human patients alleviates the symptoms of hypertension and also reverses arterial stiffness and brachial artery reactivity in type 1 diabetic patients.

 

 

and

 

High dietary taurine reduces apoptosis and atherosclerosis in the left main coronary artery...

 

In conclusion, we show that the addition of 2.5% taurine to an atherogenic diet reduces left main coronary artery wall pathology on a background of a worse lipid profile. As well, taurine also significantly reduces endothelial ER stress, hyperhomocysteinemia, and hypermethioninemia and impairs left main coronary artery endothelial cell apoptosis without detectable effects on the NOS, RAS, or oxidative stress systems.

 

 

Taking it without the atherogenic diet would presumably be even better. 

[Daniel Cooper]

Thanks for the infor Turnbuckle.  Very informative.

 

 

[William Sterog]

I take both Taurine and Vitamin K in order to prevent and reverse arterial calcification.

The vitamin K-dependent matrix Gla protein is a potent inhibitor of the arterial calcification

https://www.ncbi.nlm...ubmed/20843764/

https://www.ncbi.nlm...les/PMC3648716/

The study showed that diets high in vitamin K2 (MK-4 to MK-10) dramatically reduced the risk of cardiovascular disease and mortality (arterial calcification by 50%, cardiovascular death by 50% and all-cause mortality by 25%).

The study showed that after 3 years, arterial stiffness significantly decreased among the MK-7 group (180µg/day), compared with a slight increase in stiffness among the placebo group. MK-7 not only inhibited the age-related stiffening of the vessel walls but also reversed and reduced it.

https://www.nutraceu...fication/123944

[oipoistar]

I would be willing to finance the purchase of Tordusquemine from medchemexpress for a few people. If you have proof of arterial plaque buildup with a color doppler test and are

willing to do another checkup after using the drug and post it publicly in this thread hit me up. I'm not affiliate with the drug company i just have the same issues and would like to see

a few use-cases before taking the drug myself. 

[Daniel Cooper]

Interesting offer.  Do we even know how to administer this stuff?  IV? SubQ? 

 

In the rat study they administered it intraperitoneally.  Wouldn't want to DIY that I expect.

 

 

 

 

[Turnbuckle]

EDTA is likely a useful addition to taurine and K--

 

We hypothesize that chelating agents, such as disodium ethylene diamine tetraacetic acid (EDTA), diethylene triamine pentaacetic acid (DTPA) and sodium thiosulfate (STS) might reverse elastin calcification by directly removing calcium (Ca) from calcified tissues into soluble calcium complexes. We assessed the chelating ability of EDTA, DTPA, and STS on removal of calcium from hydroxyapatite (HA) powder, calcified porcine aortic elastin, and calcified human aorta in vitro. We show that both EDTA and DTPA could effectively remove calcium from HA and calcified tissues, while STS was not effective. The tissue architecture was not altered during chelation. In the animal model of aortic elastin-specific calcification, we further show that local periadventitial delivery of EDTA loaded in to poly (lactic-co-glycolic acid) (PLGA) nanoparticles regressed elastin specific calcification in the aorta. Collectively, the data indicate that elastin-specific medial vascular calcification could be reversed by chelating agents.

https://www.ncbi.nlm...les/PMC3809012/

 

 

 

While the oral bioavailability is low (perhaps 10%), liposomal forms are now being marketed. Or you could just take more of it.

Edited by Turnbuckle, 28 February 2018 - 11:50 AM.

[Daniel Cooper]

EDTA is likely a useful addition to taurine and K--

 

We hypothesize that chelating agents, such as disodium ethylene diamine tetraacetic acid (EDTA), diethylene triamine pentaacetic acid (DTPA) and sodium thiosulfate (STS) might reverse elastin calcification by directly removing calcium (Ca) from calcified tissues into soluble calcium complexes. We assessed the chelating ability of EDTA, DTPA, and STS on removal of calcium from hydroxyapatite (HA) powder, calcified porcine aortic elastin, and calcified human aorta in vitro. We show that both EDTA and DTPA could effectively remove calcium from HA and calcified tissues, while STS was not effective. The tissue architecture was not altered during chelation. In the animal model of aortic elastin-specific calcification, we further show that local periadventitial delivery of EDTA loaded in to poly (lactic-co-glycolic acid) (PLGA) nanoparticles regressed elastin specific calcification in the aorta. Collectively, the data indicate that elastin-specific medial vascular calcification could be reversed by chelating agents.

https://www.ncbi.nlm...les/PMC3809012/

 

 

 

While the oral bioavailability is low (perhaps 10%), liposomal forms are now being marketed. Or you could just take more of it.

 

 

That looks very interesting.  Maybe some liposomal trehalose followed by liposomal EDTA.  Thanks for the info.

 

 

[Kevinsan]

Try EDTA and Trehalose suppositories. Homemade is cheap and easy. Getting down 3g of liposomal EDTA is difficult. Acid reflux type of problem. Maybe space it out over an hour or two.

 

Anyone have experience with Plaquex infusions?

Edited by Kevinsan, 06 July 2018 - 07:49 AM.

[Acetylnordopatoninol]

it seems Trodusquemine can fully repair damage from a heart attack (and could possibly regenerate other parts of the body). here's the presentation on it by one of the researchers.

Edited by Acetylnordopatoninol, 19 August 2018 - 08:37 PM.

[mikey]

I would be in for a group buy.

 

So what happened to the notion of a group buy?

 

Trodusquemine appears to have a potentially important role in addressing CVD.

[zorba990]

Are you sure we don't just want plain old squalamine (which has the advantage of not crossing the bbb and possibly getting rid of fatty brain tissue you might want to keep, not that I have any evidence of this yet just conjecture)
https://scienceofpar.../trodusquemine/

http://www.nu-gen.ne...mg-100-capsules

Edited by zorba990, 21 August 2018 - 02:56 AM.

[Daniel Cooper]

Does squalamine make it through the digestive tract intact?

 

 

 

 

[Daniel Cooper]

Squalamine does look interesting, particularly so since it seems reasonably available.

 

But I think we need to know more about the pharmacokinetics.  Is it orally available?  What is the half life?  What is a reasonable dose and how long would you need to take it?

 

I'm not seeing tons of information posted on this compound.  Anyone having any better luck?

 

 

 

[zorba990]

Some claims of anti viral effects from squalamine
https://news.nationa...lth-squalamine/

"Squalamine Effective Against Human Viruses

In the study, squalamine thwarted infection of the dengue fever virus in human blood vessel cells and of hepatitis B and D in human liver cells—and with little harm to sharks. Shark tissue is no longer required to produce squalamine, which has been synthesized in the laboratory since 1995.

Zasloff and colleagues also discovered that squalamine inhibited yellow fever, eastern equine encephalitis virus, and murine cytomegalovirus in lab animals—in some cases curing the subjects, according to the study, published this week in the journal Proceedings of the National Academy of Sciences.

Current squalamine compounds can access only cells that have "chemical portals" to permit its entry, such as those in blood vessels, capillaries, and the liver. But a squalamine-based drug could potentially be tailored to fight a wide variety of viruses in other types of cells, he said.

The results "sounds promising" as antiviral drugs, said Todd Rider, a senior staff scientist at the Massachusetts Institute of Technology's Lincoln Laboratory and Division of Comparative Medicine.

"So far the researchers appear to have shown that squalamine is active against six viruses, although they also found that it does have some toxicity and other side effects in certain cell types at doses roughly comparable to those that were required for antiviral efficacy," Rider said by email.

"It will be interesting to see what additional viruses squalamine is or is not effective against, and whether the antiviral efficacy can be achieved without toxicity in any type of tissue."

Study leader Zasloff said, though, that all substances have some toxicity, and that clinical trials would reveal how safe the drug is for humans.

(Related: "Blockbuster Ocean Drugs on the Horizon? [2009].")

But based on its known safety so far, Zasloff predicts clinical trials for the antiviral will begin in people in about a year.

Sharks have been hiding squalamine in their bodies for 700 million years, he added. "Now it's a gift to us."

[Ovidus]

it seems Trodusquemine can fully repair damage from a heart attack (and could possibly regenerate other parts of the body). here's the presentation on it by one of the researchers.

 

BUUUUUMP!!!

 

Please check out the presentation. 

Yes the guy openly states that he founded a company to make money off of this, but the claims are out of this world.

If the same compound can have such diverse effects as reversing atherosclerosis as well as regenerating heart tissue, one wonders what other amazing things it can do. I mean this both positively and in a negative way. It is entirely possible that the compound acts very high upstream in multiple ways and may have undesirable effects too..

[zorba990]

BUUUUUMP!!!

Please check out the presentation.
Yes the guy openly states that he founded a company to make money off of this, but the claims are out of this world.
If the same compound can have such diverse effects as reversing atherosclerosis as well as regenerating heart tissue, one wonders what other amazing things it can do. I mean this both positively and in a negative way. It is entirely possible that the compound acts very high upstream in multiple ways and may have undesirable effects too..

Trodusquemine and squalamine are both present in dogfight shark liver tissue.
I suggest we have one or more such supplements assayed for Trodusquemine content.
Other than purification expense there isn't any reason trodusquemine couldn't be a supplement.

From Wikipedia :
"Trodusquemine is an aminosterol (a polyamine-steroid) similar to squalamine that is an allosteric inhibitor of PTP1B.[2][3] It was isolated from the dogfish shark by scientists at Magainin Pharmaceuticals (subsequently called Genaera) in 2000 and underwent some drug development as a potential treatment for diabetes or obesity, but the company ran out of money and closed in 200"

[Ovidus]

Trodusquemine and squalamine are both present in dogfight shark liver tissue.
I suggest we have one or more such supplements assayed for Trodusquemine content.
Other than purification expense there isn't any reason trodusquemine couldn't be a supplement.

From Wikipedia :
"Trodusquemine is an aminosterol (a polyamine-steroid) similar to squalamine that is an allosteric inhibitor of PTP1B.[2][3] It was isolated from the dogfish shark by scientists at Magainin Pharmaceuticals (subsequently called Genaera) in 2000 and underwent some drug development as a potential treatment for diabetes or obesity, but the company ran out of money and closed in 200"

 but again, even if the assay reveals there is sufficient content, how bioavailable will it be when simply swallowed?
Also, how much confidence will that assay give you? Even for that same brand there can be huge variation from one batch to another

[mikey]

From the cited paper:

 

There are a number of compounds available to the general public that inhibit PTP1B. One example is Magnolia Officinalis Extract. Assuming PTP1B inhibition is the effective cause, you might have similar success with this compound.

 

https://www.hindawi....ri/2015/139451/

 

Not expensive at all, BTW:

 

https://www.swansonv...-400-mg-60-caps

I've been taking it. Nothing exciting to write about. Dasitinib and quercetin, on the other hand, lowered my blood pressure by 15-20 points with only two exposures. But D/Q produced side-effects so that I haven't used more.

This is a "why try to duplicate the effects of Trodusquemine with something else that is unproven" kind of question? 

[mikey]

EDTA is likely a useful addition to taurine and K--

 

 

 

While the oral bioavailability is low (perhaps 10%), liposomal forms are now being marketed. Or you could just take more of it.

 

Vitamin K2 (MK-7) at 1,000 mcg/day and taurine at 3-4,000 mg a night didn't work for me. In fact, my carotid scan showed progression, not regression after a year.

 

The very honest and humble MD that administered Prolozone, which re-grew cartilage in my knees (MRI's showed this), IV hydrogen peroxide and IV ozone told me that his experience with EDTA was that it did NOT clear calcification from arteries. He could have sold it to me, but he is honest.

[Wookie]

BUMP 

 

GROUP BUY?? IM IN LETS GO!

[smithx]

Vitamin K2 (MK-7) at 1,000 mcg/day and taurine at 3-4,000 mg a night didn't work for me. In fact, my carotid scan showed progression, not regression after a year.

 

I suggest you take 5mg of K2 MK-4 per day plus 5000IU of Vitamin D.

 

That has seemed to work for me in that my CT scans showed no calcification and my father died of it at an age 19 years older than I am.

 

 

[Snapper]

Researchers from the Aberdeen study of 2017 find the same results with human blood cells.  I'm still wary of the notion of a one dose wonder drug, and whether we are talking of limiting plaque growth or reversing what's already there.  I suppose this is progress, albeit very slow progress.

 

https://www.abdn.ac.uk/news/22656/

 

[Wookie]

Researchers from the Aberdeen study of 2017 find the same results with human blood cells. I'm still wary of the notion of a one dose wonder drug, and whether we are talking of limiting plaque growth or reversing what's already there. I suppose this is progress, albeit very slow progress.

https://www.abdn.ac.uk/news/22656/

I would like to buy this or claramine.

[Wookie]

Does anyone know how to reconstitute the claramine or where I could find out? It comes as a powder. I assume it can be mixed with .9 saline for SC injection.