[ExI] Jaw-dropping CWRU Alzheimer's breakthrough?

[Jeff Davis]

2012/2/26 spike <spike66 at att.net>:

> The stoner crowd is willing take appalling risks to poke junk into their
> veins and sniff or eat god knows what, manufactured by who knows,

You could dial down this rather rough-edged characterization of "the
stoner crowd".  Overdose, disease, and despair destroy lives across
the straight<->spectrum.  Alcohol and tobacco take their toll, but
straight and sober folks can and do also crater in the face of
unsympathetic circumstance.  If you had ever gone to an Alcoholics
anonymous or narcotics anonymous meeting -- which I take it Mr.
Straight Arrow Jones has not, and I commend you for your admirable and
unblemished lifestyle -- you would have had the opportunity to look
around and notice that we're all ***just regular folks*** with our
personal particular irregularities, just trying to get it back on
track and keep it there.  Just like you ewith your current -- if more
severe -- Alzheimer's challenge.

                              <snip>

> But when
> we get a known medication taken not for kicks but to possibly defeat a
> horrifying disease, suddenly we go all wobbly kneed?  Come on, someone
> explain this to me please.

Everybody goes "wobbly" under severe stress.  An Alzheimer's problem
will do that.  But in this special bexarotene vs Alzheimer's case, the
problem is amplified.  You have great loyalty and confidence in the
"straight" system, and have (I guess) rarely strayed from the approved
path.  So going "outlaw" is scary to you.  Additional unneeded stress,
that, going against the tribe.  But as they say, "The first time is
always the hardest."

Segue.

I still don't know why Landreth kept the CWRU research results secret
until forced to publish, but
I accept as a default presumption that, at least consciously, he
thought he was the right thing.


> here’s the plan, if I can get some of this (still
> looking.)  A therapeutic dose of bexarotene is 75 mg.  My suspicion is that
> it is not completely dissolved to the molecular level in the form of
> Targretin, but I might be wrong, so my strategy is to take a tenth of that
> dose, in a form I know is completely dissolved, in about 10 grams of
> alcohol.  Then I watch and test myself for any signs of hypothyroidism or
> any increase in memory, or anything else, and I am FREEEEE of all ethical
> dilemmas, ja?

Sure, good plan.

> I cannot be faulted for taking the stuff myself, right?


As long as it doesn't make you high.  ;-}

> Cannot I pretend that it is some kind of dope, in which case our modern
> society’s notions of ethics mysteriously excuse the devourer from all
> responsibility and accountability?  Why do the stoners get a free pass but
> we amateur researchers don’t?

Oy! Take the stuff already. Just face up to the fact that your going
to become a gibbering degenerate, incapable of self-control and moral
coherence.

> Come on, my fellow extropians, toss me a bone here, offer a suggestion, talk
> me out of this if there is a good reason this is a bad idea.  Otherwise,
> suggest a place where I might get some bexarotene.

On day one, I Googled up at least two Chinese suppliers who deal in
kilogram quantities.  Send them an email, ask price, and a spec sheet
detailing purity level and impurity concentrations.

>  I feel like I am sailing
> uncharted waters alone.

You are most definitely in uncharted waters and just as definitely not
alone.  There are 5.4 million Alzheimer's sufferers and probably 40 or
50 million of their friends all in the boat with you, shrouded in the
mists of Maya.

Segue.

Blood brain barrier.

>From Wikipedia re bexarotene this comment:

Mechanism

Bexarotene is a retinoid specifically selective for retinoid X receptors,...
RXRs are located primarily in visceral organs such as the liver and kidney.
                       ***********************
As the CWRU study shows efficacy on the other side of the murine BBB,
we can conclude that either bexarotene crosses the murine BBB, or that
it doesn't need to.  That ApoE is upregulated and reduces dissolved
amyloid beta levels where that is (presumably) needed, is
demonstrated.  Start there, re its effect across the human BBB, and go
and collect some (human) data.

Segue.

It seems to me that bexarotene, if it has a comparable effect in
humans as in mice, will be more a preventive, and a means to halt
progression, than a cure.

Human Alzheimer's is thought to be asymptomatic for the first ten to
fifteen years.  So for people at high risk -- those possessing ApoE
allele 4 -- or with the development of a means of early --
pre-symptomatic -- diagnosis, bexarotene could be employed as a
preventive.

Rolling back more advanced Alzheimer's, which involves neurofibrilary
tangles, tau proteins, and nerve cell death -- all of which are not
found in the mouse model -- is clearly a follow on challenge, and one
on which the effect of bexarotene is currently a zero-data zone.

That's it for now.

Very curious to find out the Kg price for Chinese reagent grade
bexarotene.  Do tell us when you find out.

Best, Jeff Davis

      "Everything's hard till you know how to do it."
                                 Ray Charles