
Parents of kids with rare disease found a promising drug - shawndumas
http://arstechnica.com/science/2016/04/sweet-drug-clears-cholesterol-reverses-heart-disease-and-was-found-by-parents/
======
kazinator
> _Typical treatments include statins and other cholesterol-lowering drugs,
> which are not always effective, particularly when patients don’t adhere to
> doctor-prescribed, low-cholesterol diets._

Must an otherwise good article perpetuate the tired bullshit about dietary
cholesterol.

A piece of white bread topped with sugary jam (optionally on top of margarine)
is a low-cholesterol snack.

Just because cholesterol shows up from what you ate doesn't mean that, say,
statins aren't working; maybe you're just throwing off the method by which
their effectiveness is _indirectly_ gauged.

~~~
pygy_
I know it doesn't have an impact in healthy people, but what about people with
hypercholesterolemia?

I don't know if it is the case, but it sounds plausible that the drugs that
regulate endogenous production like statins would only be effective in the
absence of an external supply (since they don't affect the way cholesterolemia
is regulated).

~~~
pygy_
Expanding on this:

Cholesterol is a key culprit in atherosclerosis, not just a marker. It
accumulates in the walls of blood vessels in the form of fibro-fatty plaques
that are responsible for angina, infarctus, stroke etc.

The reason why it accumulates has not been completely elucidated (related to
endothelium stress, caused by toxins like tobacco and bacteria that break in
into the blood because of gingivitis).

The higher the level of cholesterol (especially LDL [†]) in the blood, the
more plaque forms and the more one is at risk of consequences (plaque
formation is rate-limited by cholesterolemia (blood cholesterol levels)).

Cholesterolemia in physiological conditions is independent of intake. If the
body is in demand, the liver will synthetise cholesterol de novo in the
absence of dieatary intake.

I don't think we know at this point what drives the demand, but we've
developed drugs that work well on the innner supply end, namely statins, that
block the production of cholesterol by the liver. They are, however,
ineffective if you eat boatloads of cholesterol.

\----

† Recent findings seem to show that HDL is not in itself protective, and that
high levels of HDL (that are correlated with fewer complications) may be a
passive marker of another protective process.

~~~
jasonparallel
My father and I both have hdl levels that are 2 to 3 times higher then our
ldl. We both also have Gilberts syndrome so I was hypothesising that it might
be related but have not been able to find any research. Do you have links to
these recent finding around the processes causing high hdl?

~~~
pygy_
No link, but an experimental drug that moderately lowers LDL and dramatically
raises HDL was recently abandoned after clinical trials showed no health
benefits.

EDIT: H => L. hrrmm...

------
dnautics
This is amazing. The unfortunate thing though is that the effectiveness of
cyclodextrin on NPC (versus atherosclerosis) might not hold up to scrutiny - I
remember the NPC finding when it first came out almost a decade ago (worked in
a lab that was interested in NPC) but more recent experiments have thrown the
result into question.

It's kind of strange that this hasn't been proposed before - when you buy
cholesterol for scientific experiments, it's often encapsulated in
cyclodextrin, that product has been around for a while.

[edit:] found this
[http://www.tandfonline.com/doi/abs/10.1080/10717540050120205...](http://www.tandfonline.com/doi/abs/10.1080/10717540050120205#.VwbYtSZyhyQ)
so someone has investigated it before, at least.

------
jrapdx3
Article certainly piques my curiosity, unfortunately the paywall it's behind
impedes getting the whole story. How often have we seen "breakthroughs" fail
to live up to expectations, in this case not yet enough info to have any idea
how it's likely to turn out.

An interesting side-note here is that cholesterol itself has "detergent-like"
properties similar to the cyclodextrin agent. That is, both molecules have
hydrophilic and hydrophobic ends, which enables stabilizing lipid droplets
floating in an aqueous medium like the bloodstream. I suppose cyclodextrin
properties will vary with molecular weight and conformation, but never would
have guessed it would have the basic characteristics described.

Always amazes me where discoveries come from, goes to show it isn't always
high-cost, specialized research that leads the way.

------
aab0
Beware surrogates. An apropos bit of news from a few days ago:
[http://www.nytimes.com/2016/04/04/health/dashing-hopes-
study...](http://www.nytimes.com/2016/04/04/health/dashing-hopes-study-shows-
cholesterol-drug-has-no-benefits.html)
[http://blogs.sciencemag.org/pipeline/archives/2016/04/04/cet...](http://blogs.sciencemag.org/pipeline/archives/2016/04/04/cetp-
finally-heads-to-the-trash-heap)

Cyclodextrin may be useful for Niemann-Pick disease, where the cholesterol
itself is the immediate proximate cause of the problem, but if it's already
clinically-approved and has been used, where are the heart attack
correlations?

~~~
mathgeek
> but if it's already clinically-approved and has been used, where are the
> heart attack correlations?

I read is as being used currently, but the "breakthrough" being administration
through IV. I'm not sure if that's correct, was just my interpretation.

------
refurb
Fantastically little information provided, yet it's called a "breakthrough!!".

How is the drug dosed? If it's oral, then I'm not surprised. It probably traps
the cholesterol in the mouse-model diet before it can even be absorbed.

~~~
aaronbrethorst
FTA:

    
    
        They found cyclodextrin and initially tried using it in
        oral doses, which is known to be safe. However, the 
        chemical couldn’t effectively reach the brain that way.
        The couple made headlines with their tireless efforts to
        get drug companies, the FDA, and doctors to let them try
        out intravenous treatments of cyclodextrin for their
        twins—and they won. Regular treatments gradually
        improved—although didn’t cure—the twins’ conditions.
        Cyclodextrin is now in clinical trials to treat other
        kids with NPC.

~~~
dekhn
This interesting approach just raises more questions than it answers;
experiments with sample size n=1 being run by non-medically trained
individuals are unorthodox and generally suspect in the modern medical
climate.

~~~
aaronbrethorst
here's another experiment for you that I've run on myself:

When I consume products that contain wheat, I feel sick. When I don't, I feel
fine. Sample size n=1, and I am not medically trained. What conclusions, if
any, do you think I can draw from my experience?

~~~
dekhn
I don't know, did you control for placebo effects? Did you verify there isn't
something else in those products that makes you feel sick?

Science is hard. Control experiments are key.

