
UAB cures diabetes in lab mice, preparing for human trial - waterlesscloud
http://wiat.com/2014/11/06/uab-cures-diabetes-in-lab-mice-preparing-for-human-trial/
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kristopolous
I know a number of people who have diabetes and not vast financial resources
(including the family of a teenaged nephew of mine). The current medical
solution takes a significant and ever-present financial toll on them.
Something like this would be absolutely life changing for those people who
can't easily afford on-going, lifetime treatment.

I really hope it works.

~~~
ars
I wonder how many will not wait for the study and just try it.

It's not a cheap drug though - about $0.75 per pill.

~~~
dmd
$0.75 seems incredibly inexpensive to me. Modafinil, by comparison, can be $50
per dose.

~~~
xeroxmalf
Or even on the higher end, some MS drugs like Copaxone can be upwards of $200
to $300 per dose.

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thinkcomp
This seems to be research related to Type I diabetes, which means it's only
potentially a cure for one variant of the disease, and it's also not totally
clear how it differs from previous research:

[http://link.springer.com/article/10.1007%2FBF00626359#page-1](http://link.springer.com/article/10.1007%2FBF00626359#page-1)

Nonetheless, it does seem that there have been a number of encouraging
research finds around Type I diabetes in recent months
([http://news.harvard.edu/gazette/story/2014/10/giant-leap-
aga...](http://news.harvard.edu/gazette/story/2014/10/giant-leap-against-
diabetes/)).

In general, always take media coverage of scientific finds with a grain of
salt, and maybe two grains for local news coverage.

~~~
zaroth
I think the research you linked is for T2D (non-insulin dependent). It's
interesting the research into Verapamil apparently is for _both_ T1 and T2,
since my understanding was the mechanism of the diseases were entirely
different.

With T1D your body stops producing insulin due to beta cell death caused by an
autoimmune disorder, so you need to constantly monitor your blood glucose
level and carb intake in order to dose yourself with the right amount of
insulin multiple times per day, or you go into hypo/hyperglycemia.

I'm much less familiar with T2D, but I thought the body produces more and more
insulin but becomes resistant and the insulin fails to adequately control
blood glucose level. Beta cell death in T2D is then a follow-on confounding
factor due to the persistently high glucose levels.

Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many
differences, few similarities:
[http://www.ncbi.nlm.nih.gov/pubmed/16306347](http://www.ncbi.nlm.nih.gov/pubmed/16306347)

~~~
coldpie
Yes. It is always frustrating to have to dig through paragraphs of text to
find out which of the two, basically unrelated diseases the article is talking
about.

I really wish they had different names.

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micro_cam
T1 diabetic and former diabetes researcher here.

This is interesting but curing diabetes in mice has been done so many times it
is hard to get too excited. It turns out mice are better at regrowing things
then us.

That said i have borderline high blood pressure and am tempted to try this.

[1] in an extreme case: [http://singularityhub.com/2010/05/11/the-incredible-
regenera...](http://singularityhub.com/2010/05/11/the-incredible-regenerating-
mouse/)

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bayesianhorse
My concern is: If it were that "easy", why hasn't anybody noticed an increase
in "spontaneous remissions" of diabetes in people being treated with
verapamil?

It may just have gone unnoticed, but there should be thousands of diabetes
patients who were treated with verapamil because of high blood pressure.

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andrewstuart
Anyone know why apparently so many things work on mice but not people? Apart
from "cause mice aren't people" of course.

~~~
dnautics
I can give a hypothetical reason why specifically might not work (disclaimer:
my PhD thesis is in this field). In most Type I diabetics, the autoantigen (as
in the protein that is the target of immune attack) is this peptide called
amylin. This peptide is a generally problematic peptide - it's metastable -
and in Type II diabetics it forms plaques. Interestingly, mice and rats have
amylin, but unlike most other mammals, it's not metastable[0]. I would not be
surprised if in NOD (non-obese-diabetic) mice it's NOT the autoantigen.

Based on different protein targetting, the mechanism of beta-cell killing in
NOD mice might not have exactly the same autoimmune interactions, and a
rejuvenation strategy might not work in humans quite the same way.

It's not entirely clear to me when they plan on doing therapeutic intervention
for children with Type I diabetes; by the time first symptoms show up it may
be too late (unlike the mice where they knew when/that it would happen).

Finally, it's a bit odd to me that they didn't look through health records of
existing type I diabetes patients that have been incidentally prescribed
Verapamil. There should be some usable data that hints at the possible
usefulness of this strategy, unless the patients were treated for hypertension
much later in life than getting diabetes (very likely), aka too late to do
anything about it.

[0]mice and rats are weird, they also have two copies of the insulin gene. One
of the copies has an amino acid that is absolutely conserved across all
vertebrates substituted for a substantially different one.

[1] bonus: rats also don't have gall bladders.

[2] bonus 2: While I was working on diabetes model systems in the lab, we had
lots of verapamil floating around, because my boss had this crazy idea that
verapimil would fix a whole category of diseases (calcium homeostasis is
important for protein folding in the endoplasmic reticulum).

~~~
bigtunacan
No PhD here, but IAMA T1D.

I noticed from the actual study that candidates for the trial must be within 3
months of diagnosis to even be considered; so it seems they are trying to
screen and find only those people who have just recently developed diabetes
and reverse it early in the process. In a sense this is sort of like catching
a soon to be T2D in the pre-diabetic phase and telling them to eat less and
run more. (There is no offense intended in that previous statement; with an
obese pre-diabetic (type 2) it is possible to stop the disease before things
are too late through exercise and diet, this is not the case in with a Type
1).

This makes me question if this is an effective treatment ONLY when caught
early; or if it could be useful for long time diabetics like myself.

Also this treatment addresses beta cell replacement which is one side, but it
doesn't address the autoimmune side which is actually causing the beta cell
destruction in the first place. So would this be a lifetime pill that is taken
to continuously build new beta cells? As I see it in the autoimmune T1D case
as the beta cells remain under attack this would not be a "cure" per se, but
rather an ongoing treatment that would result in an overall better outcome and
quality of life for a diabetic (given it works at all).

~~~
dnautics
you pretty much nailed all of my concerns about this (especially the
pernicious concern about maintenance drugs), but if it works, hey, that's
better than nothing.

~~~
bigtunacan
Yeah; if I could take a pill a day like the T2D crowd with Metformin I would
prefer that any day to insulin therapy.

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orofino
Anyone else find the fo us on the article solely on "Alabamians" a bit odd?

~~~
gabemart
The website WIAT.com is for the radio station WIAT 42 based out of Birmingham,
Alabama.

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ars
Why go directly to double blind trial?

Shouldn't you first do some open label tests and see if there _appears_ to be
any difference, and only then _prove_ it with a double blind?

Seems like that approach would save money.

~~~
zaroth
Double-blind makes no sense to me either? T1D doesn't just go away. If the
treatment works, it would be obvious...

Verapamil was approved by the FDA in 1982, so I would assume safety is well
established.

~~~
cperciva
> Double-blind makes no sense to me either? T1D doesn't just go away. If the
> treatment works, it would be obvious...

They're not just interested in whether T1D "goes away". If insulin
requirements drop or A1c %s improve, those would also be useful results
(either innately, or as a "look, there's something going on here, we just need
to fine tune the dosage"). You can't get good data on those if patients'
behaviour is influenced by unblinded treatment.

> I would assume safety is well established.

You can't assume that when you're dealing with smaller populations. For
example, short courses of corticosteroids are very safe in the general
population, but can cause life-threatening hyperglycaemia in diabetics. So
they have to look for side effects; and if they're looking, they need the
trial to be blinded in order to avoid seeing a side effect which doesn't
really exist.

~~~
zaroth
I remember there was a great post a few weeks back about double-blind
controlled trials being used in neonatal care, and the difficulty in getting
the medical community to accept double-blind randomized trials over the last
several decades. So I don't want to discount the validity of the method. [1]

But just to belabor the point, couldn't you detect the impact on A1C or a
dropping dosage pretty quickly? Everything's logged on the meter/pump/CGM, so
you would have an extensive baseline to compare to....

Oh I just realized they want to test this on _newly diagnosed patients_. Hmmm,
in that case I can see more the need for this. I wonder how much the
"honeymoon" period would confound the results -- with my son we saw vast
changes in required dosages throughout the first year. Not to mention it takes
a while to get a handle on how to deal with it, and in the meantime... errors
in handling, dosing, mis-counting carbs, etc... combined with honeymooning, I
don't know how you could make heads or tails of a newly diagnosed T1D's
numbers in just one year, unless the result is very significant.

I wonder why they don't test on people with well controlled T1D. I hope it
doesn't imply it's something like AAT where it only possibly works if started
soon after onset. I guess it's reasonable to expect early treatment after
onset could be more effective, so maybe that figures into their strategy.

[1] -
[https://news.ycombinator.com/item?id=8490442](https://news.ycombinator.com/item?id=8490442)

~~~
cperciva
They're doing this on newly diagnosed patients because that's where they hope
to see results: This isn't expected to be a cure so much as a "honeymoon
extension" solution -- they're looking at preventing further beta cell
destruction, not creating new beta cells.

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bitL
Just curious if this is true - I read somewhere that during WW2 long-term
starving people (months) were able to cure their diabetes. There was also some
paper about a drastic diet that allows pancreas to regenerate itself and
resume normal insulin production. Can someone please shed light on this? Does
this work on some subset of diabetes? Or is it just a hoax/unknown?

~~~
svsaraf
It isn't true. Insulin was discovered in the early 1900s, but before it was
used, starvation would extend the lifespan post-diagnosis from weeks to
months, if that. After that, the patient would die of starvation.

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agumonkey
It's interesting that they found a cure for the root issue.

