Homotaurine (tramiprosate) appears to be a structure corrector

[Brian4]

Ah, darn, I'm sorry to hear that. When do you take your last dose of the day? Reading through some papers here –

https://pubmed.ncbi.nlm.nih.gov/?term=homotaurine+gaba

– is making me think that homotaurine could actually help my (chronic) early-waking insomnia, if I time the dosing right. My reasoning is: if it functions as a significantly strong GABA-receptor agonist (though probably only at one type of GABA-receptor), then I could take it 2-3 hours after falling asleep (when I literally always wake up to pee), and it would function like a z drug (Ambien-like drug) with a short half-life (such as zaleplon), and get me through the "last-mile" sleep problem that has cursed me for over a decade.

If your last dose is at dinner time or earlier, it's possible that you're experiencing reduced GABA signaling as the homotaurine leaves your system 6-9 hours later.

[Tincup]

Ah, darn, I'm sorry to hear that. When do you take your last dose of the day?

It was earlier in the day. Thank you for this! I will pay very close attention to timing. I was doing 150mg (3 pills) morning and then later. Trying to do 100 mg three times wasn't happening as my daily life schedule is always changing.

I posted recently about my failure trying to replete iodine. After looking at my data, my consultant told me that I wasn't "holding onto" any of the iodine I was consuming and gave me suggestions to correct this. Germane to the sleep discussion, when I mentioned my chronic waking, he said he was that way for 30 + years and after getting iodine replete, he sleeps well though the night for 8 hours. I'm just now restarting the protocol from the beginning. This includes stopping the iodine & doing 2 weeks of a salt loading protocol along with supplemental nutrients & cofactors before restarting the iodine. The purpose is to deplete my system of excess bromine slowly with the salt prior to taking the iodine. The iodine will displace the bromine quickly as both are halides. This can be detrimental and cause bromism. The Cl from the NaCl will do this much more slowly. Once I restart the iodine, it will likely take some/many months to become iodine replete. If it changes my sleep, I will report on it.

[LisaJS]

https://molecularneurodegeneration.biom ... 23-00620-9

This is amazing news. It would explain why trials show an allele-dose effect (homozygote > heterozygote > non-carrier).

Although note that an older paper suggests that the molecule being corrected is Aβ42:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488121/

Homotaurine may of course be correcting both.

I'm taking 100 mg t.i.d. Experiencing the unfortunately common nausea side effect, but hoping that will go away soon.

Brian

Hi Brian,

I’m a 47 year old E4 homozygote without any noticeable symptoms of cognitive decline. Wondering if I should consider starting homotaurine now as prevention or wait until phase 3/long term data comes out since I still (hopefully) have some time before cognitive decline sets in. What are everyone’s thoughts on this?

Lisa

[Brian4]

Hi Lisa,

People have different risk tolerance, but this would be my perspective: It's great to be born with the APOE-ε4 variant. Two copies is better than one. The evidence is mixed, but, overall, it seems to confer a neurological developmental advantage, in particular under conditions of low nutrient availability, but probably, to some degree, even under conditions of good nutrition.

At some point in life, having the ε4 variant becomes a neurological disadvantage. We don't know when this happens. It may happen very early, even in one's teens, though of course it will vary from person to person. We don't know. But at some point it's a good idea to switch to ε3 or ε2, if that were possible. I imagine that the ideal time to "switch variants" is, at the latest, once the brain is fully developed, somewhere in one's mid-20s.

Taking homotaurine looks as though it might be a way to achieve a functional change in isoform, without gene therapy. In other words, it could be a way to achieve the same thing as switching variants. So, myself, I would start taking it before turning 30.

Brian

[LisaJS]

Hi Lisa,

People have different risk tolerance, but this would be my perspective: It's great to be born with the APOE-ε4 variant. Two copies is better than one. The evidence is mixed, but, overall, it seems to confer a neurological developmental advantage, in particular under conditions of low nutrient availability, but probably, to some degree, even under conditions of good nutrition.

At some point in life, having the ε4 variant becomes a neurological disadvantage. We don't know when this happens. It may happen very early, even in one's teens, though of course it will vary from person to person. We don't know. But at some point it's a good idea to switch to ε3 or ε2, if that were possible. I imagine that the ideal time to "switch variants" is, at the latest, once the brain is fully developed, somewhere in one's mid-20s.

Taking homotaurine looks as though it might be a way to achieve a functional change in isoform, without gene therapy. In other words, it could be a way to achieve the same thing as switching variants. So, myself, I would start taking it before turning 30.

Brian

Hi Brian,

Thanks for taking the time to share your perspective. I had to read the first part over a couple of times; « it’s great to be born with the APOE-e4 variant ». I thought it was a typo, but I see what you’re saying. It’s an advantage in early life and a disadvantage later. But happily it seems like it may be reversible with homotaurine.

I can’t seem to find any for sale in Canada. Any fellow canucks out there who can share their source? Is taurine a decent substitute, because it’s readily available from health food stores here. Thanks again for your help! I’m new to this world and it’s so valuable to have more knowledgeable and experienced guides with the same motivating factor.

Lisa

[Julie G]

For anyone who's experienced nausea with homotaurine, any helpful tips?

[Brian4]

Julie, sorry to hear about the nausea. My protocol (see earlier in this thread -- in sum: don't take on empty stomach except at bedtime, with the exception of 50 mg upon waking) has worked for me, but I do sometimes experience a bit of nausea after my waking dose. I took 100 mg this morning upon waking, just as an experiment. I definitely am feeling the nausea right now. I can live with it, but it's not so fun. Let's hope ALZ801 gets approved soon!

[Julie G]

Julie, sorry to hear about the nausea. My protocol (see earlier in this thread -- in sum: don't take on empty stomach except at bedtime, with the exception of 50 mg upon waking) has worked for me, but I do sometimes experience a bit of nausea after my waking dose. I took 100 mg this morning upon waking, just as an experiment. I definitely am feeling the nausea right now. I can live with it, but it's not so fun. Let's hope ALZ801 gets approved soon!

Thanks for the tips. Yeah, the nausea is no fun. My morning dose (taken while fasting) has progressed beyond that... ew! Interestingly, my nighttime dose never causes an issue and even appears to help with sleep. I think you're right, it's a matter of ensuring you take it with food, which is tough with an OMAD eating schedule.

[Fiver]

Hi Brian and Julie. I hope all is well. Thanks for this thread. I hadn’t been following these studies, though I love seaweed natural products I ordered some myself and will join this growing nausea-avoidance experiment. Fingers crossed!

[Julie G]

Hi Brian and Julie. I hope all is well. Thanks for this thread. I hadn’t been following these studies, though I love seaweed natural products I ordered some myself and will join this growing nausea-avoidance experiment. Fingers crossed!

Good to hear from you, my friend! Yes, I sincerely hope you avoid my experience- blah