UAB cures diabetes in lab mice, preparing for human trial | Hacker News Reader

UAB cures diabetes in lab mice, preparing for human trial

wiat.com

112 pointswaterlesscloud48 comments

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.

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.

A heck of a lot cheaper than insulin, test strips, needles, or CGMs, pumps, etc. The clinical trial is 1 pill once a day. $300 / year versus upwards of $10,000 / year.

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

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

$0.75 per pill is super cheap especially for a novel treatment. What are you talking about dude?

Blood glucose test strips are about $0.25 per strip and most diabetics test themselves multiple times per day. Anyone using insulin will pay substantially more per day.

$0.75/pill seems like a steal.

Yep. On my insurance plan, I spend about $250 per month on Type I Diabetes supplies. That adds up.

An interesting side effect of how insurance plans are structured where I work finds the people with diabetes or recurring medical expenses are usually better off on the HSA plans offered as the go to 90/100% payment of costs once the yearly deductible is met.

Considering the hassles that my mom has with medicaid/medicare (not sure exactly which one it is) since the ACA with obtaining her insulin and possible cure is great news. She actually has to plan trips around shipping dates because some supplies will not ship unless X number of days passed. Worse, the costs went up. Between insulin, the pump, test strips, and mandatory examinations, its not an easy road.

That adds up to $3000 per year. That adds up to $300,000 per century. That adds up to $3,000,000 per millennia. That adds up to $35,144,750 since the beginning of the Holocene epoch.

These days, the costs of addition are out of control.

It varies a lot, though. My T1D supplies (as a college student on my parents' insurance) cost more like $50-$75 a month.

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

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...).

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

Yes beta cells killed by the immune system is Type I.

It's also important to point out that Type I only makes up about 5% of diabetes cases. Though a cure for either would drastically improve a lot of peoples lives.

Is type II treatable by lifestyle changes, or are the effects permanent once it occurs?

Type 2 is treatable by lifestyle changes. The specifics can very person to person based on genes, the time for which you have had it and so on, it is largely possible to use lifestyle modification to get off medication and have your average sugars under control and basically enter the pre-diabetic stage.

At http://www.janacare.com/, we are using technology to help this process.

I can't even imagine what my life would be like without T1D. I've had it for almost 20 years now. The constant monitoring, the general feeling of crappiness, the extreme costs. I spend thousands of dollars a year on the costs.

Any given sickness can have catastrophic effects as well. When I have a flu, I usually check myself into the hospital for monitoring. Blood sugar fluctuates hard, and its difficult to keep food down. My dad's best friend died from exactly this, a normal flu that disrupted eating patterns.

Literally ANY mistake can be life threatening. Over the last year I have been required emergency care twice due to low blood sugars. I would pay anything, do anything to have this go away.

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

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.

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...

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.

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

This page gives a good summary as to why mice are used in research:

http://research.jax.org/mousegenetics/advantages/advantages-...

Humans have far more variation in environment, they think relatively independently (making sticking to a prescribed regimen less likely), and they are far more complex organisms in general.

Lot's of things we think we know but don't and chemical space is super large? Why a molecule works within a mouse but not human, depends on what you mean by doesn't work. It might not be that it doesn't work but that the potential drug never makes it that far in the process for other reasons. Common reasons would be poor ADMET issues and difficulty in formulation for enteral route.

edit for other route Al Mann spent almost a billion and 20 years on inhalable insulin and only recently found success.

Also, works is a matter of interpretation. Better relative to other drugs on the market? Shows better outcomes than no treatment? There are some drugs out there that with time and more investigation are showing some lack of efficacy, eg gliptins

Because you can experiment on them and keep iterating till you find what works.

They also have short lives, so you don't have to wait long to see if some new treatment works.

One reason is that "cures X in mice" doesn't actually mean "cures X in mice" -- it usually means "cures X in mice which have a genetic mutation which causes them to always develop X". (And sometimes it means "cures X in mice to which we have surgically performed X", e.g., X = spine severing.)

For example, studies of type 1 diabetes usually take place in BB rats (http://en.wikipedia.org/wiki/Biobreeding_rat) or NOD mice (http://en.wikipedia.org/wiki/NOD_mice). These animals are known to exhibit the symptoms of type 1 diabetes; but we don't know if their disease progression exactly matches that of humans with type 1 diabetes (and we can't know, because we don't know exactly how type 1 diabetes progresses in humans). It's entirely possible that a cure for NOD mice simply blocks a disease pathway which doesn't occur in humans anyway.

Good point, but a minor nitpick: using X to represent multiple things, especially in the same sentence, is confusing. You could always use other letters, like Y!

To my eye, the previous comment was using X to represent the same thing, at least within each individual phrase. (Plugging in "X=spine severing" into both uses in that example seems to work just fine, for instance.)

Ah, I suppose you're right. I guess my brain automatically rejected the notion of "cures spine severing", so assumed it must be something different. Apologies to parent!

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).

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).

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.

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

"apparently so many things work on mice but not people?"

If we experimented on people (tho it would take longer) we would probably find lots of things that work on people but not mice.

Nobody complains about us keeping lines of various knockout mice you can order from a catalog. Nobody has a problem with us killing them when it's time to passage the cells. It's not an issue when we create stress responses by burning their feet. No problem when we inject them with toxins, bacteria, viruses, foreign cells, and a host of other things so we can watch how long it takes for them to die.

I say this as someone who is a proponent of the murine model. I think animal models are incredibly valuable to science and we wouldn't be where we were without them. That said, imagine all the things I described being performed on humans... I don't think that would go over so well.

A "nonfatal" lab setup wouldn't yield the same kind of results. You would be greatly limited to the scope of what you could investigate. Many experiments kill out of necessity. Also for the sake of throughput. Most of the experimental mice lines are doomed simply by the fact they lack critical immune function--we stock them that way for the sake of isolating experiments to a particular immune system function. Scientific abstraction. (And for reproducability. They're standardized equipment, if you will.)

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

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

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.

Time is probably a significant constraint. Better to waste a million dollars on a trial which could have been avoided than to delay the discovery of a cure by two years.

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.

> 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.

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

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.

I'm looking up the clinical trial description (check out ref. 1) but I think these researchers are moving directly to a double-blind study because this drug is already FDA-approved (ref. 2).

Typically, clinical trials occur in three phases (ref. 3). Since this drug's side effects have been studied, the researchers are moving directly to test the drug's effects.

As a final point, open label studies suffer from bias due to a person's expectations of improved health. A double-blind study minimizes this. Why spend money on a biased test that you'll need to redo instead of just doing the right test the first time?

[1] clinicaltrials.gov

[2] http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm1729...

[3] http://clinicaltrials.gov/ct2/help/glossary/phase

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?

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.

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

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