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Celebration Thread! Homotaurine/Tramiprosate supplement

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
J11
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Celebration Thread! Homotaurine/Tramiprosate supplement

Postby J11 » Sat Aug 29, 2020 11:10 am

Homotaurine2.GIF
Homotaurinet.GIF
Sorry everyone I realize that this has been talked about on other threads, though it is just too good not
to repost. Homotaurine has been in development for years and years. Yet, the results in the figure below
are large. 120%? Yeah! Oral inexpensive supplement? Unbelievable. Works in 44? Why, yes!
34? Not as sure.

We know from other trials that a ~1.3 point treatment effect on CDR is big.
In the figure this was enough to almost entirely stop decline.
Of course, generation 2 of this product has even greater brain availability.

There is just so much great news that is on the horizon and has already arrived.
Simultaneously targeting multiple amyloid pathways is already highly plausible.
Will the new frontier no longer be stopping AD, but reversing it?
Then add in tau inhibitors? Yea!

Update, gains were sustained out for another 52 weeks (130 weeks) in the trial extension.

Wow!!!
"In APOE4/4 patients, tramiprosate 150mg BID exhibited sustained cognitive and functional benefits over 2.5 years,
compared to the “delayed start” group who initially received placebo."

Nice if they could have shown us the figure, the write-up is somewhat confusing about the actual results.
Has this result been published?

https://alzheon.com/clinical-effects-tr ... ion-study/

Here is the link for free journal articles on Tramiprosate. These were hard ones to find (for free anyways).
https://www.jpreventionalzheimer.com/al ... tml?search

Um, we really aren't supposed to push products here, but 11 pounds for homotaurine? 35% discount today.
Is there going to be any payola left for me at 11 pounds? No?
https://www.supersmart.com/en/shop/brai ... ement-0661




https://alzheon.com/clinical-data/
https://alzheon.com/wp-content/uploads/ ... _91918.png
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Last edited by J11 on Sun Aug 30, 2020 12:13 pm, edited 2 times in total.

DoubleBond
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Re: Celebration Thread! Homotaurine/Tramiprosate supplement

Postby DoubleBond » Sat Aug 29, 2020 12:59 pm

That's really very exciting, J11,! Thanks for posting it.

Immediately, questions come to my mind:

1) The dose used was 150 mg twice per day, i.e. 300 mg per day. I see at least one commercially available homotaurine supplement:
https://us.supersmart.com/article.pl?id=0661
It costs $17 per 3,000 mg, so basically, for $1.70 per day, one can get the dose used in the trial. Has anyone tried it?

2) Also, homotaurine is very close to taurine - as Wikipedia says these two differ only by an extra carbon in the chain of homotaurine. Of course, this extra carbon may make a big difference. Me and my wife are already taking taurine for its cardiovascular benefits. Has anyone investigated the cognitive action of taurine for 4/4s or other populations? Would taurine interfere with homotaurine when both are taken simultaneously?

J11
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Re: Celebration Thread! Homotaurine/Tramiprosate supplement

Postby J11 » Sat Aug 29, 2020 1:59 pm

Thank you, DoubleBond.
I thought there would be a fair number of people who were not aware of how powerful the results were;
even I needed a reminder.

Sometimes we really do need a blaring tabloid headline to capture our attention.


120% reduction in AD progression?

All this boiler plate blah blah effective blah blah AD blah treatment blah found
doesn't do it.

AD Cured !!!


Space Aliens have landed!
As a present to the people of planet earth they offer us a cure for AD!
see page 3.

This does.
That ought to make people sit up and take notice.
I need bigger a font to say how massive it is!

These clinical trials go on and on forever and you start to lose track of the results.
It seems that when you do not hear back for a while that something is happening.
This also happened with methylene blue.
It took them ~10 years to publish the phase 2 results and it also was startling.

I would stay with homotaurine.
Changing a single molecule in chemistry can make a big difference.
Considering how reasonably priced homotaurine is, I do not see the benefit in trying taurine
which (I am guessing) hasn't been tested in AD.

With homotaurine you really need to keep in mind what the competing product aducanumab is offering.
trami with the 44s at week 78 had a 1.24 CDR-SB benefit over placebo in the figure above.
aducan with Emerge had a 0.76 CDR-SB benefit in the total high dose group (n=127) over placebo (n=297) at week 78.

trami is an orally administered inexpensive derivative of seaweed with few side effects (though, side effects have included
upset stomach, etc.) .
aducan is administered IV and has ARIA side effects in upwards and beyond 50% of patients especially 44s.

Yet, putting those two together might be quite powerful as both of them appear to work through different amyloid mechanisms.
Add in methylene blue (inhibitor of tau the driving pathology of AD)?
Things certainly start to look very interesting.

Let the celebration begin!!!
Last edited by J11 on Sun Aug 30, 2020 12:17 pm, edited 1 time in total.

DoubleBond
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Re: Celebration Thread! Homotaurine/Tramiprosate supplement

Postby DoubleBond » Sat Aug 29, 2020 2:09 pm

Thanks for the reply, J11. Very encouraging. I can imagine that the big pharma companies are not very interested in testing the inexpensive, unpatentable products such as homotaurine or methylene blue.

Do you happen to know why homotaurine is not being sold by US supplement producers? The only distributor of homotaurine that is showing in my Google search is supersmart.com, based in Europe (they are shipping to the US).

J11
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Re: Celebration Thread! Homotaurine/Tramiprosate supplement

Postby J11 » Sat Aug 29, 2020 3:09 pm

DoubleBond, yes but the great irony is that these have been and are being tested by the little pharma companies.
Alzheon (tramiprosate/ALZ-801) and taurx (LMTX/methylene blue)

Little pharmas can quickly become big pharmas when they can bring to market products that address critically
important medical problems such as AD.

It is important that some sort of economic incentive signal be sent to these companies so they know that their products will have a market economic value acknowledged by the tens of millions of people who are currently struggling with AD and the at least hundreds of millions of others who worry that they will.

There is so much gratitude and good will out there for the company that can solve the AD pandemic that there really should not be
a great deal of concern that the AD community will walk out without paying the tab.

SuperSmart.com appears to be a monopoly supplier of homotaurine pretty much everywhere in the anglosphere.
I have no problem if somewhere Alzheon is setting the terms for its distribution: it's their product they have spent
$200 million developing it. I am grateful to them. An AD product with this much treatment effect especially for 44s
is worth more than $17. If this is basically an underground monopoly situation, then I am also grateful that they are
not trying to maximize revenue by limiting supply. When you send out that much positive energy into the universe,
good things start to happen for you.

I just stepped up and dropped 17 large on homotaurine. Makes a great deal of sense to me.

The problem that often arises with the big pharmas is that they try to maximize price and then minimize revenue.
When I suggested to people that I suspect have or are near to having AD that all they will need to slow their decline is write a check for $100,000 per year once the first wave of anti-dementings reach the market; they simply did not think that this was a reasonable option. How is pharma behavior revenue maximizing? Alzheimer's is so universally present in the community that it is not sensible to think of the market as a few thousand people (as can often be true of modern breakthrough pharmaceuticals) but hundreds of millions.

In the last few days the NIH has stepped up with ~ $50 million to advance ALZ-801 in clinical trials. When you have a solid product, then sooner or later other stakeholders will start paying your tab because these others often can have truly enormous costs that could be reduced if they were to work with others. [Edit: This might actually have a more ominous interpretation. Possibly private
investment is now steering clear of new Alzheimer's targets because the first wave of anti-amyloids is nearing market entry. How could you justify investing in AD research when LMTM can essentially stop progression? Treatments that could help rebuild the brain (possibly through neurogenesis), though, would be greatly appreciated.
Last edited by J11 on Sun Aug 30, 2020 12:28 pm, edited 1 time in total.

J11
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Re: Celebration Thread! Homotaurine/Tramiprosate supplement

Postby J11 » Sat Aug 29, 2020 3:22 pm

OK, I will repost the other APOE4 forum threads and comments about homotaurine here, so it is all in one handy location. That is actually quite interesting below in the "Tramiprosate, again" thread it was noted that even in 2018 homotaurine was not available in the US. Back then everyone wanted to move to Canada. Perhaps the mass migration spooked, immigration; ergo, stateside availability.

There has not been enough posted about homotaurine on our forum.
This is a large large product that has been obscure to too many.
It is currently available and reasonably it should combine with other
products that might gain approval.

Ironically, taurx has found that typical AD medications interfere with efficacy of
newer treatments. Perhaps the same thing happened with homotaurine.
Possibly removing standard of care could produce a better result?
This would be a question possibly best left to clinical trials; hopefully
Alzheon is on this one.

Tramiprosate, again (thread)
viewtopic.php?f=4&t=4552&p=53932&hilit=homotaurine#p53932

Tramiprosate: a silver bullet for 4/4 carriers? (thread)
viewtopic.php?f=16&t=3702&p=47349&hilit=homotaurine#p47349

An Introduction (thread)
viewtopic.php?f=2&t=3371&p=40453&hilit=homotaurine#p40453

Phase 3 studies of tramiprosate in the subgroup of Alzheimer’s disease (AD) patients with APOE4/4 genotype (thread)
viewtopic.php?f=16&t=1764&p=19953&hilit=homotaurine#p19953

Alzheon Announces Efficacy Outcomes (thread)
viewtopic.php?f=4&t=1757&p=19952&hilit=homotaurine#p19952

homotaurine posts
viewtopic.php?f=16&t=3948&hilit=homotaurine

homotaurine post (Tue Feb 04, 2020 8:06 am)
viewtopic.php?f=4&t=6858&p=75032&hilit=homotaurine#p75032

homotaurine post (Mon Nov 13, 2017 9:25 pm)
viewtopic.php?f=16&t=5533&p=61200&hilit=homotaurine#p61200
Last edited by J11 on Sun Aug 30, 2020 12:30 pm, edited 1 time in total.

J11
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Re: Celebration Thread! Homotaurine/Tramiprosate supplement

Postby J11 » Sat Aug 29, 2020 3:45 pm

hmm, that's fairly interesting I went to the wayback and the first webcrawl for SuperSmart is April 2018. I have not been able to find the homotaurine page for it as of yet. Does anyone know how long SuperSmart has been selling homotaurine for? Perhaps it did not start until ~early 2019?

J11
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Re: Celebration Thread! Homotaurine/Tramiprosate supplement

Postby J11 » Sat Aug 29, 2020 4:59 pm

Has Alzheon done a GWAS with Alz-801/tramiprosate?
Some 33s, 34s and 44s might have more or less amyloid style
AD dependent upon their non-4 genotypes. It would be interesting
to have this question clarified. This might more finely define
those who will be in the response class.

Perhaps now that homotaurine is out in the wild those with AD
could do this themselves. Possibly even here on forum.
A gene chip file and some psychometric measurements.
Would be helpful if we had a computerized high quality
validated (and free) AD psychometric tool do this.
Considering the overwhelming social costs involved
it is somewhat surprising that we don't.
Others who want to help can enable the solution
by providing the basic tools-- in the internet age
that might be all that is required, the AD community
could take it from there if the high hanging fruit were
made to be low hanging fruit.

J11
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Re: Celebration Thread! Homotaurine/Tramiprosate supplement

Postby J11 » Sat Aug 29, 2020 5:04 pm

homotau44.GIF


This is the combined result for the tramiprosate phase IIIs in 44s.
This gives us a better feel for the overall result. So they are chasing after
the mild 44 sub-sub-group. The CDR as we have seen is quite a good
instrument in measuring AD decline. In the aducan phase III it was remarkable
seeing the CDR tracing amyloid removal perfectly, while the changes in MMSE were
almost random.

I will be interested to see the study design for the Alz-801 phase III. Early or very early
(MMSE ~27 ?). Perhaps they could even use the ADCOMS. If you intend to go early it is
important to have a test that is sensitive to early changes.

I magnified the results from the above figure. The CDR benefit in the 44s contracted to ~0.80 from
the first slide of ~1.24. The figure in this post uses a bigger sample, so this is perhaps a better estimate.

Will also like to crunch through the 34 results.

I also tend to agree with others who say that we should focus less on the cognitive (with MMSE and CDR) and more on the
functional. When you get to the point where you have to ask someone if they know what day it is,
the answer might not be that important. What is important from the perspective of a caregiver is helping
the person with their functional activities of daily living-- the ADCS-ADL is what you are looking for.
aducan actually had a fairly good result on this scale.

One problem here is that the functional impairment at such an early stage really is not all that noticeable. We are typically talking about instrumental activities of daily living such as can discuss current affairs etc.. From the caregiving point of view this instrumental loss is not a large stress.

I have been looking around further on the Alzheon site. The phase III trial is going with n=150 arms in placebo and ALZ-801. They believe in it. Would be good if they defined what early AD is, I do not see this mentioned. It really is a smart idea to go with 44 stratified genotype. It is surprising that this has not been done before. Everyone chased after the whole AD market and yet were loading up the trial with a great many patients (30%?) who did not even have AD. Those with epsilon 44 and cognitive impairment very likely have AD. Effective AD drugs would have arrived years and years sooner if other clinical trials had used this genetic selection approach. We as the APOE4 forum should have been more vocal on this issue. It did not make sense not to do such selection. They really should consider using ADCOMS as the cognitive readout, it appears to be a very sensitive test in early AD. With that test they might even choose to go earlier, though sometimes there can be confusion about whether going earlier really is the best plan.
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J11
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Re: Celebration Thread! Homotaurine/Tramiprosate supplement

Postby J11 » Sat Aug 29, 2020 7:53 pm

This shows how the chemical structure of tramiprosate relates to that of ALZ-801.
Adding some extra carbons to the end is an often used technique
to enhance effectiveness and reset patentability.

It is nonetheless interesting how much greater the concentration of ALZ-801 reaches than does tramiprosate (~double).

Chem.GIF




This is taurine.

taurine.GIF
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