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

spike spike66 at att.net
Mon Feb 20 21:19:11 UTC 2012


I had one hell of an insight and I need some input from the medical
hipsters, for I am a rocket scientist, not a doctor.

Last week I studied into the solubility of bexarotene and learned that 75mg
in the form of Targretin is therapeutic and safe for humans.  The capsules
themselves look a little like vitamin E softgels, so that is a huge clue.  I
know that it takes a couple ounces, or about 75 grams of alcohol to dissolve
75mg of bexarotene, so the active ingredient is definitely not dissolved in
either alcohol nor dimethyl sulfoxide in Targretin.  Eisai Corp has figured
out some means of dissolving bexarotene in some kind of gel or solvent oil
for delivery in such a way that the medication perfuses the body.

It occurred to me that bexarotene in the form of Targretin might perfuse the
body but not permeate the blood/brain barrier, whereas it might go across
the barrier if dissolved in alcohol.  Reasoning: we know that the solubility
of bexarotene in water is nearly negligible and that its natural state is
powder.  So pure bexarotene clumps together in globs of millions of
molecules, forming a fine powder.  So if one swallowed 75 mg of bexarotene
in powder form, it would still be in powder form when it arrived several
days later at the sewage processing plant.  

Now imagine if bexarotene in some form of oil solvent partially dissolves,
forming a slurry or suspension of globs of tens of thousands of molecules.
Then it can enter the bloodstream in that form, and (somehow) have a
therapeutic effect on skin cancers, but still not be able to cross the blood
brain barrier?  If so, then the finding that Targretin is safe would not
apply to bexarotene in alcohol?

If so, then we would have no reason to suspect that the 100k patients taking
Targretin would see any impact on Alzheimer's, since the medication doesn't
cross the barrier.  But if dissolved in alcohol, perhaps the medication
could get to where the action is.

That brings up another thorny question.  Targretin has been shown to be safe
in 75 mg doses, but only in the form of a slurry or suspension in solvent
oil (or whatever they are using as a solvent, not alcohol or DMSO.)  So
there is a risk that if we took 75 mg of bexarotene, dissolved it in alcohol
and the patient glugged it down, that same 75 mg might kill the patient.

As far as I can tell, the mice were given bexarotene in a form that was
administered via a skin permeant, not via Targretin, since the article
mentions skin surface area.  When I see the volume of a Targretin tablet, I
suspect that the bexarotene may be in a form that cannot permeate into the
brain, which is perhaps why Targretin is safe to use.  So after ten days of
internet eerie silence, we still don't know what bexarotene does in the
brain.  75mg might kill the patient.  

This is one hell of a note, ja?  I am now in a position where I would give a
family member FDA approved Targretin, but would not give that same family
member 75mg of bexarotene dissolved in alcohol.

Dr. Smigrodzki, or some of you hipsters, how do we experiment ethically with
this?  Is it even possible to experiment ethically with bexarotene mixed
with alcohol?  Can we use aged chimps or something?   Heeeelllllp Mister
Wizaaarrrrd! 

spike



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