Replies to post #180237 on Anavex Life Sciences Corp (AVXL)

[Investor2014]

I believe it throws some new light on things, although the subject matter is also not within my core competencies.

The fact that the endogenous, the body's own, Sigma-1 Receptor agonists have not been fully understood and therefore what and how the firetruck is called from the station when there is a fire, makes it more difficult to understand the actual MOA of A2-73.

I think the paper, among other things, may offer some clues to why Donepezil, having higher binding to S1R, seems to work less well than A2-73.

[nidan7500]

I know nothing about the subject matter, way over my head. Is the article good for AVXL.

I could be wrong but am thinking that NO ONE KNOWS ALL this stuff but we seem to eventually find a collective body of knowledge (BOK) that works. We also note that occasionally someone comes along who claims to know everything and disagrees w/the consensus. That is why we have an IGNORE function. BTW, not agreeing is usually OK, it's about how, not what.

[Biostockclub]

Childbearing women produce greater amounts of choline... see link contained.


Interesting link, GAB. Thanks for posting that find!

In my opinion “Is it good for AVXL?”, yes, it could help understand and explain our compound vis a vis other sigma 1 receptor agonists, such as donepezil, in its ability to TREAT Alzheimer’s Disease.

However, sadly, it does not adequately account for the glaring statistic that women suffer AD 2:1 over men, and therefore, if one is searching for the CAUSE, this doesn’t get us there.

Note the levels of choline in females and males in this article which presents contradictory evidence to the Jan 9, 2019 study findings:

https://academic.oup.com/ajcn/article/92/5/1113/4597519

Females during childbearing years produce more choline. Pregnant and breastfeeding women produce less choline and require slightly more (through supplements). Men produce less as do postmenopausal women and require even greater levels of supplementation.
> The implication being that men would suffer AD at higher rates - barring supplementation. We know this is not the case.

This is because choline is derived from estrogen. (From my cite)

But, the original cite, the Jan 9 study, notes that progesterone is a “notable” S1r binder with no extracellular stimuli affecting regulation (occupies/binds but has no effect and therefore inhibits other agonists such as choline from binding and agonizing.)

If true, as stated, this does not get us to the disparity of the prevalence - male/female, does it?

My assessment is that this is encouraging in the treatment of disease (the business Anavex is in), but has not unlocked the cause, YET.
I say “yet” because I anticipate literature linking progesterone’s role as a recurring temporary blocker/inhibitor which presents an opportunity for protein misfolding to occur repeatedly and marinate over years, as this will now be seen as a necessary dot to connect. Once that link is made, the cause will become clearer.
At which time, the FDA and BP’s and early movements by organizations championing the approval of birth control pill contraception for women will be in the position of “they knew not what they wrought”. The sigma 1 was not known of - they could not have foreseen this coming.
Be careful what you ask for, you might get it....that’s a high price to pay, imo.

Two cents,
Bio
And, as long as we are being scientific, the groundhog predicts an early spring! :)