[ExI] medical ethics question, was: RE: Medical power of attorney for cryonicsts

Rafal Smigrodzki rafal.smigrodzki at gmail.com
Fri Dec 5 03:45:16 UTC 2014


On Thu, Dec 4, 2014 at 4:02 PM, spike <spike66 at att.net> wrote:

>
> Dr. Rafal, you are probably the best qualified person here to comment, not
> on the specific scheme (considering your professional standing I would not
> recommend that) but rather on the medical ethics aspects.  Right now you
> are
> my wise older brother (who is younger than I am) and I will most likely do
> whatever you suggest.
>

### I tend to think first of all like a doctor or a biologist, only
secondarily as an ethicist. First I'd think hard about the biology, and
what is the actual likelihood of helping, only after coming to conclusions
at this level would I explore the ethical implications.

First of all, murine models of AD are completely, 100% worthless. The whole
amyloid story is a bum steer, something that should have been expunged from
handbooks decades ago, but still persists, zombie-like, thanks to inertia
and fear of losing face. See here:

http://triviallyso.blogspot.com/2009/07/malleus-amyloidarum.html

I penned this years ago but still stand behind it.

This said, who knows: RXR receptors modulate mitochondrial function, which
is undoubtedly mechanistically involved in the so-called AD (sporadic AD is
not really AD, only a group of age-related dementias with superficial
resemblance to true AD, which is an early onset familial disease). The
precise cause of this dysfunction is not completely clear but fixing it
might do some good. There is very little in the literature on bexarotene
and mitochondria but see here:

http://www-ncbi-nlm-nih-gov.proxy.library.vcu.edu/pubmed/18755147

Bexarotene is anti-apoptotic and upregulates catalase, reduces ROS. So,
maybe it could work. The thyroid suppression is a typical side effect of
drugs that boost mitochondrial function (thyroid boosts mitos, so boosted
mitos use negative feedback to suppress thyroid, this is system control
101). So, maybe bexarotene could work but again, not because of the mouse
results but for other reasons.

If your doctor is willing to try, he should have first a thorough
neuropsych evaluation, so we have a handle on his objective level of
functioning. In this way, some of the placebo effect can be controlled.
After a few months on bexarotene he gets re-evaluated, and there is an
objective measure of cognitive function. He keeps checking his thyroid
(TSH, free T4, free T3), take thyroid hormones if needed. Also, keep an eye
on cholesterol levels, they can go up on bexarotene. If his cognitive
function follows the usual declining trajectory of AD, or worse, he stops
the medication, no or little harm done. If his cognitive function stays
surprisingly good, we have a story.

Here is an interesting study:

http://www-ncbi-nlm-nih-gov.proxy.library.vcu.edu/pubmed/24434091

Bexarotene helps with schizophrenia, another metabolic, mitochondrial
disease (I have a hammer and I see nails everywhere :))

Ethically, grown-ups should be able to try anything they want: Jumping out
of airplanes without parachute (see it on YouTube), eating 16 whole hotdogs
without chewing (don't waste your time seeing it on YouTube), fixing their
AD with plausible-sounding drugs, whatever. It is right and proper for
smart, well-meaning, reasonable people to try their best to understand
mysteries and try to sail through dangerous seas. As long as nobody is
selling snake oil, there is no question of unethical exploitation of the
weak and desperate. 'Nuff said.

Rafał
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