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.
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:
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.
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.
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.
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).
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.
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
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?
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.
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.
[+] [-] kristopolous|11 years ago|reply
I really hope it works.
[+] [-] ars|11 years ago|reply
It's not a cheap drug though - about $0.75 per pill.
[+] [-] coldpie|11 years ago|reply
[+] [-] thinkcomp|11 years ago|reply
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.
[+] [-] zaroth|11 years ago|reply
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
[+] [-] xxs|11 years ago|reply
[+] [-] micro_cam|11 years ago|reply
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...
[+] [-] bayesianhorse|11 years ago|reply
It may just have gone unnoticed, but there should be thousands of diabetes patients who were treated with verapamil because of high blood pressure.
[+] [-] andrewstuart|11 years ago|reply
[+] [-] dnautics|11 years ago|reply
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).
[+] [-] cperciva|11 years ago|reply
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.
[+] [-] thinkcomp|11 years ago|reply
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.
[+] [-] drmilsurp|11 years ago|reply
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
[+] [-] nmeofthestate|11 years ago|reply
If we experimented on people (tho it would take longer) we would probably find lots of things that work on people but not mice.
[+] [-] ars|11 years ago|reply
They also have short lives, so you don't have to wait long to see if some new treatment works.
[+] [-] orofino|11 years ago|reply
[+] [-] unknown|11 years ago|reply
[deleted]
[+] [-] gabemart|11 years ago|reply
[+] [-] ars|11 years ago|reply
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.
[+] [-] ejstronge|11 years ago|reply
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
[+] [-] zaroth|11 years ago|reply
Verapamil was approved by the FDA in 1982, so I would assume safety is well established.
[+] [-] cperciva|11 years ago|reply
[+] [-] bitL|11 years ago|reply
[+] [-] svsaraf|11 years ago|reply
[+] [-] agumonkey|11 years ago|reply
[+] [-] hospes|11 years ago|reply
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