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Trodusquemine Reverse Plaque - Group Buy Share Data

arterial plaque trodusquemine msi-1436 cardiovascular disease coronary arteries carotid arteries calcification mouse study cancer diabetes

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#31 Daniel Cooper

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Posted 09 September 2018 - 10:41 PM

Inhibition of PtP1B by trodusquemine (MSI-1436) Causes Fat-specific Weight Loss in Diet-induced Obese Mice

 

 

 


Edited by Daniel Cooper, 09 September 2018 - 10:41 PM.

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#32 mikey

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Posted 09 September 2018 - 10:46 PM

 

In case we haven't posted this one:

 

The protein tyrosine phosphatase 1B inhibitor MSI-1436
stimulates regeneration of heart and multiple other tissues

 

 

Yet another reason to support an MSI-1436 group buy. Heart tissue regeneration is only one of the groups of tissues that might benefit.

Thank you, Daniel Cooper.



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#33 Daniel Cooper

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Posted 09 September 2018 - 10:53 PM

First in Human Use of MSI-1436 (Trodusquemine), a Centrally and Peripherally Acting Selective PTP1B Inhibitor

 

 


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#34 mikey

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Posted 09 September 2018 - 10:57 PM

Well it's being touted as safe and any immediate and serious side effects such as hypercalcemia, hypercholesterolemia, or hyperlipidemia would presumably have been detected, so whatever it's doing, if we decide to be optimistic, is leading to rapid elimination or extensive metabolism of the byproducts of plaque breakdown. Perhaps the foam cells in this scenario are able to produce conditions that rapidly degrade these byproducts by enzymatic action? I think it is easy to assume that our immune cells (which create the plaque in the first place) are able to digest a nice range of toxic materials, and that perhaps that range is extended by the Trodusquemine by the removal of a few important lynch pins that we lack or the activation of genetics that may have been silenced by aging.

 

 

Thank you for chiming in, YOLF.

 

We need to understand what is happening so that we can determine the application to humans.

 

This molecule apparently has global effects, perhaps as it affects genes that translate a complete regeneration of a system or systems in the body. What does it do? How does it do what it does? 



#35 mikey

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Posted 09 September 2018 - 11:13 PM

Thanks for uploading that article.

It seem that they are synthesizing the compound themselves. Their synthesis seems pretty straightforward and has high yields, although they seem to be a little cryptic on details, referring to other articles, which then reference other articles for the specific information. It seems as though we'll have to have a custom synthesis done.

There are a few labs in China that I trust, though we now have some tariffs importing from there and China is now imposing environmental fees (a good thing).

 

After having someone that worked in labs in China for years report here that he would NEVER order anything from China I am concerned about ordering from China.

 

We have several labs in the US that can do the synthesis. I will have my assistant collect a list of labs tomorrow and begin the job of pricing. Just begin, since we don't know how many will join the group buy yet. 



#36 mikey

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Posted 09 September 2018 - 11:17 PM

Dosing for humans in the breast cancer study (that was terminated because the sponsor company went "belly-up" - seven dosing schedules:

 
Arms and Interventions
 
Go to  pulldown.png

 

Arm  Intervention/treatment  Experimental: MSI-1436C (Trodusquemine) 20 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 20 mg/m2. Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 26 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 26 mg/m2. Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 34 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 34 mg/m2 . Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 44 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 44 mg/m2 . Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 57 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 57 mg/m2. Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 74 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 74 mg/m2 . Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 96 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 96 mg/m2 . Drug infusions will last approximately 2 hours.

 

 

This is a starting point to determine what is appropriate for humans, hopefully orally, but also SubQ.



#37 The Capybara

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Posted 09 September 2018 - 11:39 PM

An interesting article on herbal PTP1B inhibitors:

 

https://www.scienced...221169115002440

 

Good find on the I.V. dosages proposed for the human study.

I have to wonder why the compound is referred to as "MSI-1436C" rather than just "MSI-1436"

MSI-1436 is a freebase and I would guess has low solubility. Perhaps MSI-1436C is a salt, or maybe the freebase in some sort of surfactant.



#38 Daniel Cooper

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Posted 09 September 2018 - 11:43 PM

PTP1B inhibitors are so relatively common in nature I wonder if that truly is the underlying method of action that is causing this atherosclerosis reversal.  It appears that a single dose may be sufficient to cause this effect and some of these effects seem to be durable in the long term after a single or limited number of doses. 

 

 

 



#39 The Capybara

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Posted 09 September 2018 - 11:44 PM

There are many trustworthy Chinese labs. Many with ISO and/or GMP certification.

You can always run samples through a third party lab for purity testing.

China now makes a lot (perhaps most) of US generic drugs, though they are "laundered" through pharmaceutical companies in India prior to importation to the US.


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#40 YOLF

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Posted 10 September 2018 - 12:35 AM

 

Dosing for humans in the breast cancer study (that was terminated because the sponsor company went "belly-up" - seven dosing schedules:

 
Arms and Interventions
 
Go to  pulldown.png

 

Arm  Intervention/treatment  Experimental: MSI-1436C (Trodusquemine) 20 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 20 mg/m2. Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 26 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 26 mg/m2. Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 34 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 34 mg/m2 . Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 44 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 44 mg/m2 . Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 57 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 57 mg/m2. Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 74 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 74 mg/m2 . Drug infusions will last approximately 2 hours.
Drug: MSI-1436C
Dose escalation, single intravenous infusion twice a week for 3 weeks on a 4-week cycle.
Other Name: Trodusquemine
Experimental: MSI-1436C (Trodusquemine) 96 mg/m2 IV
Open label, interventional, dose escalation of MSI-1436 (Trodusquemine), single intravenous infusion twice a week for 3 weeks on a 4-week cycle. Subjects will receive MSI-1436 at a dose of 96 mg/m2 . Drug infusions will last approximately 2 hours.

 

 

This is a starting point to determine what is appropriate for humans, hopefully orally, but also SubQ.

 

I wonder how realistic it would be for a group of us to put together the human resources needed to qualify for orphan drug funding. I'd like to do that with alot of stuff actually. I'm not sure how much the situation fits, but I think it would be worth looking into and getting involved as a community investment opportunity... I hate how funding kills the potential of good drugs where the lack of funding is determined by the portfolio diversity concerns of the investors. Blockbuster drugs seem to die this way and we could basically do this kind of thing in such a way that we're all getting diagnostic testing and get access to a wealth of information. I think group buyers should definitely get involved in this capacity and that we should perhaps consider ways of funding the preliminary work and creating the investment opportunity for our members and guinea pigs and 70kg rats.



#41 Daniel Cooper

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Posted 10 September 2018 - 02:01 AM

Mikey,

 

I'm curious as to why this group buy thread ended up in the "Forum Issues" section and whether it might get more visibility if you requested a forum admin to move it someplace else like "Supplements"?

 

 

 



#42 classicstrat

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Posted 10 September 2018 - 03:24 AM

I'd be interested provided the cost is affordable.

#43 mikey

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Posted 10 September 2018 - 05:17 AM

There are many trustworthy Chinese labs. Many with ISO and/or GMP certification.

You can always run samples through a third party lab for purity testing.

China now makes a lot (perhaps most) of US generic drugs, though they are "laundered" through pharmaceutical companies in India prior to importation to the US.

 

It makes cents (pun intended) if buying from a Chinese lab AND the cost of testing for the molecule and TFA's (purity) is less than it cost to buy it from a US lab.

Either way, really, we should have tests done on what we buy before using. There are some US labs that we probably don't need to test, as they have long established track records.

 

I have to get my list of labs out so that we can get bidding. If you know of any Chinese labs that we might get bidding from, please present a short list.

 

So, a Chinese lab may make sense on those grounds. 



#44 The Capybara

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Posted 10 September 2018 - 05:18 AM

I wonder how realistic it would be for a group of us to put together the human resources needed to qualify for orphan drug funding. I'd like to do that with alot of stuff actually. I'm not sure how much the situation fits, but I think it would be worth looking into and getting involved as a community investment opportunity... I hate how funding kills the potential of good drugs where the lack of funding is determined by the portfolio diversity concerns of the investors. Blockbuster drugs seem to die this way and we could basically do this kind of thing in such a way that we're all getting diagnostic testing and get access to a wealth of information. I think group buyers should definitely get involved in this capacity and that we should perhaps consider ways of funding the preliminary work and creating the investment opportunity for our members and guinea pigs and 70kg rats.

 

In this case, since it's not a controlled substance, if the patent was dropped, expired, transferred to the public domain, you could synthesize this compound and it would be classified as a supplement.
 



#45 mikey

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Posted 10 September 2018 - 05:24 AM

I wonder how realistic it would be for a group of us to put together the human resources needed to qualify for orphan drug funding. I'd like to do that with alot of stuff actually. I'm not sure how much the situation fits, but I think it would be worth looking into and getting involved as a community investment opportunity... I hate how funding kills the potential of good drugs where the lack of funding is determined by the portfolio diversity concerns of the investors. Blockbuster drugs seem to die this way and we could basically do this kind of thing in such a way that we're all getting diagnostic testing and get access to a wealth of information. I think group buyers should definitely get involved in this capacity and that we should perhaps consider ways of funding the preliminary work and creating the investment opportunity for our members and guinea pigs and 70kg rats.

 

Great thinking, YOLF.

 

I support this and will work to effect it, but I need coaching or just working on a team with some knowledgeable people that are dedicated to doing this.

Another thing, but I don't know how practical it is - that we work up a loosely defined "study" so that it might be published.

 

If this produces significantly good effects, even if they're barely better than anecdotes, we want to share the information as widely as possible for the good of humanity.



#46 mikey

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Posted 10 September 2018 - 05:27 AM

Mikey,

 

I'm curious as to why this group buy thread ended up in the "Forum Issues" section and whether it might get more visibility if you requested a forum admin to move it someplace else like "Supplements"?

 

I didn't know any better when I started this, but I will reach out to a forum admin to ask. Good thinking.



#47 mikey

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Posted 10 September 2018 - 05:30 AM

I'd be interested provided the cost is affordable.

 

 

We now have eleven potential group buyers.



#48 Daniel Cooper

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Posted 10 September 2018 - 02:34 PM

In this case, since it's not a controlled substance, if the patent was dropped, expired, transferred to the public domain, you could synthesize this compound and it would be classified as a supplement.
 

 

 

I'll bet if you look at that patent it's an application patent.  Given that this is a natural compound found in dogfish I seriously doubt they were able to patent the molecule.

 

I'll also bet that's why Genaera's funding ran out.  Not because the compound didn't show promise, but because application patents are notoriously weak and easy to circumvent.



#49 Daniel Cooper

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Posted 10 September 2018 - 03:32 PM

Here's at least one of Genaera's patents:

 

 

A method for treating rapamycin induced diabetes-like syndrome using trodusquemine

 

As I suspected, this is an application patent, not a patent on the molecule.

 

 

 


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#50 mikey

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Posted 10 September 2018 - 08:00 PM

First in Human Use of MSI-1436 (Trodusquemine), a Centrally and Peripherally Acting Selective PTP1B Inhibitor

 

 

Very good, Daniel. This is the safety study that showed it safe in humans. Seminal!

 

Thank you!



#51 YOLF

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Posted 10 September 2018 - 08:00 PM

I'll bet if you look at that patent it's an application patent.  Given that this is a natural compound found in dogfish I seriously doubt they were able to patent the molecule.

 

I'll also bet that's why Genaera's funding ran out.  Not because the compound didn't show promise, but because application patents are notoriously weak and easy to circumvent.

 

It's still important to develop these things as pharmaceuticals otherwise people just won't know about them. We know about them b/c we go looking for ourselves and doctors are generally going to reject the efficacy of anything that hasn't been FDA approved through the usual processes or which lack social engineering sales teams, free continuing education credits, or that kind of thing. Not to mention it would be covered by insurance if it were an approved Rx, thus making insurance useful for rejuvenation. 

 

I've got solutions to make it work.



#52 mikey

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Posted 10 September 2018 - 11:25 PM

It's still important to develop these things as pharmaceuticals otherwise people just won't know about them. We know about them b/c we go looking for ourselves and doctors are generally going to reject the efficacy of anything that hasn't been FDA approved through the usual processes or which lack social engineering sales teams, free continuing education credits, or that kind of thing. Not to mention it would be covered by insurance if it were an approved Rx, thus making insurance useful for rejuvenation. 

 

I've got solutions to make it work.

 

Hello YOLF,
I will support any likely solution, in whatever role I am equipped for - AND this kind of thing gives me a reason to live, which is paramount to the extension of healthy lifespan.

 

Please PM me or post as you prefer.

 

Kind regards,

Michael



#53 mikey

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Posted 10 September 2018 - 11:53 PM

In this case, since it's not a controlled substance, if the patent was dropped, expired, transferred to the public domain, you could synthesize this compound and it would be classified as a supplement.
 

 

If this occurred and it was able to be classified and sold as a supplement I am interested in participating, having expertise in the formulation, production, and marketing of "supplements." 

And rather than I alone profiting from its sales I would prefer an "Aquarian" solution, which is that a group that truly works together to accomplish disseminating this potentially societally beneficial "supplement" shares profits as a community effort, with a bow (1%) to benefit a non-profit organization, such as Habitat For Humanity.

This, I believe, would engender the co-operation of a number of complementary minds.

 

Thank you for inspiring this notion, Cabybara.



#54 mikey

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Posted 11 September 2018 - 12:20 AM

If someone can find the source of trodusquemine cited in:

Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine.

that would be a great help!

It might be in Materials and Methods section, but it'll be somewhere.

I don't have access to the full article, but if you're at a university chances are......

 

Here is the full text.

It says that they synthesized it as was done in another study -  Zasloff, M., Williams, J. I., Chen, Q., Anderson, M., Maeder, T., Holroyd, K., Jones, S., Kinney, W., Cheshire, K., and McLane, M. (2001) A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties. Int. J. Obes. 25, 689− 950 697.

 

There is a file error for the full text that I downloaded for "A spermine-coupled cholesterol...." I will work to attach the second file in another post.



#55 Daniel Cooper

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Posted 11 September 2018 - 12:51 AM

If this occurred and it was able to be classified and sold as a supplement I am interested in participating, having expertise in the formulation, production, and marketing of "supplements." 

And rather than I alone profiting from its sales I would prefer an "Aquarian" solution, which is that a group that truly works together to accomplish disseminating this potentially societally beneficial "supplement" shares profits as a community effort, with a bow (1%) to benefit a non-profit organization, such as Habitat For Humanity.

This, I believe, would engender the co-operation of a number of complementary minds.

 

Thank you for inspiring this notion, Cabybara.

 

Since Zasloff's group originally isolated trodusquemine from dogfish liver I don't know why you couldn't sell this as a supplement, but I'm hardly an expert in this area.



#56 Daniel Cooper

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Posted 11 September 2018 - 12:58 AM

It's still important to develop these things as pharmaceuticals otherwise people just won't know about them. We know about them b/c we go looking for ourselves and doctors are generally going to reject the efficacy of anything that hasn't been FDA approved through the usual processes or which lack social engineering sales teams, free continuing education credits, or that kind of thing. Not to mention it would be covered by insurance if it were an approved Rx, thus making insurance useful for rejuvenation. 

 

I've got solutions to make it work.

 

I don't know if it's important to develop this substance as a pharmaceutical or if we'd be better off with it sold as a supplement.

 

I suppose that if it is developed as a pharmaceutical we'd get real human trials where they'd have to prove both safety and effectiveness, which would definitely be something.  But, the cost would be higher and we would have doctors as gatekeepers to this compound.

 

Obviously if it is developed as a supplement we're far less likely to get any good human trails.

 

Maybe it could be developed along the lines of Nicotinamide Riboside at Chromadex.  They do have the research horsepower and the funds to do some reasonable human trials.



#57 YOLF

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Posted 11 September 2018 - 01:19 AM

I don't know if it's important to develop this substance as a pharmaceutical or if we'd be better off with it sold as a supplement.

 

I suppose that if it is developed as a pharmaceutical we'd get real human trials where they'd have to prove both safety and effectiveness, which would definitely be something.  But, the cost would be higher and we would have doctors as gatekeepers to this compound.

 

Obviously if it is developed as a supplement we're far less likely to get any good human trails.

 

Maybe it could be developed along the lines of Nicotinamide Riboside at Chromadex.  They do have the research horsepower and the funds to do some reasonable human trials.

I'm saying do both. Make it pharma and supplement. Ideally your doctor Rx's it to you for something and for it's clinical applications it is both insurance sponsored (healthy/young people actually get something out of healthcare) and gains pharmaceutical status as well as develops our community into an engine for drug development for things which would not otherwise be readily available without FDA approval such as all the research chemicals we go dolly over. 

 

In the process we also gain access to these things and a better idea of how well it works and where it fits into total rejuvenation.

 

NR is great, but how many people take it? How many people could have healthier lifestyles if they did? How many won't b/c their doctor didn't recommend it or b/c they are expecting the pharmaceutical solution to be the right solution? 



#58 Daniel Cooper

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Posted 11 September 2018 - 01:24 AM

Well, I'd certainly like to see it commercially available without having to wait a decade to get it through the FDA.  Whatever it takes.

 

The FDA has become such an impediment to medical technology development.

 

 

 


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#59 YOLF

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Posted 11 September 2018 - 01:39 AM

Well you can be part of the study group in the meantime :)



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#60 docmaas

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Posted 11 September 2018 - 07:50 PM

I'm interested.  







Also tagged with one or more of these keywords: arterial plaque, trodusquemine, msi-1436, cardiovascular disease, coronary arteries, carotid arteries, calcification, mouse study, cancer, diabetes

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