8 ms·

UAB cures diabetes in lab mice, preparing for human trial

112 points by waterlesscloud 12y ago

kristopolous 12y ago
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 12y ago
  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.
  - zaroth 12y ago
    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.
  - dmd 12y ago
    $0.75 seems incredibly inexpensive to me. Modafinil, by comparison, can be $50 per dose.
    - xeroxmalf 12y ago
      Or even on the higher end, some MS drugs like Copaxone can be upwards of $200 to $300 per dose.
  - thathonkey 12y ago
    $0.75 per pill is super cheap especially for a novel treatment. What are you talking about dude?
  - evilduck 12y ago
    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.
- coldpie 12y ago
  Yep. On my insurance plan, I spend about $250 per month on Type I Diabetes supplies. That adds up.
  - Shivetya 12y ago
    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.
  - falsestprophet 12y ago
    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.
  - georgef 12y ago
    It varies a lot, though. My T1D supplies (as a college student on my parents' insurance) cost more like $50-$75 a month.
andrewstuart 12y ago
Anyone know why apparently so many things work on mice but not people? Apart from "cause mice aren't people" of course.
- thinkcomp 12y ago
  This page gives a good summary as to why mice are used in research: http://research.jax.org/mousegenetics/advantages/advantages-of-mouse.html 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 12y ago
  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
- ars 12y ago
  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.
- cperciva 12y ago
  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 http://en.wikipedia.org/wiki/Biobreeding_rat) or NOD mice (http://en.wikipedia.org/wiki/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 12y ago
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-against-diabetes/ 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.
- xxs 12y ago
  Yes beta cells killed by the immune system is Type I.
  - nhstanley 12y ago
    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.
    - ars 12y ago
      Is type II treatable by lifestyle changes, or are the effects permanent once it occurs?
      - ratpik 12y ago
        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/ http://www.janacare.com/, we are using technology to help this process.
    - pdoconnell 12y ago
agumonkey 12y ago
It's interesting that they found a cure for the root issue.
orofino 12y ago
Anyone else find the fo us on the article solely on "Alabamians" a bit odd?
- deleted 12y ago
  [deleted]
  - nwndarkness 12y ago
    This article is related to curing Type 1 diabetes which has nothing to do with obesity.
- gabemart 12y ago
  The website WIAT.com is for the radio station WIAT 42 based out of Birmingham, Alabama.
ars 12y ago
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.
- cperciva 12y ago
  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.
- zaroth 12y ago
  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 12y ago
    > 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 12y ago
      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
bitL 12y ago
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 12y ago
  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.
hospes 12y ago
Since this drug was used since 1982, I wonder if it is necessary to start human clinical tests. They can first analyze data on people with diabetes who have been taking this medicine for high blood pressure.
micro_cam 12y ago
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-regenerating-mouse/ http://singularityhub.com/2010/05/11/the-incredible-regenera...
bayesianhorse 12y ago
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.

112 points by waterlesscloud 12y ago

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 12y ago
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.
- zaroth 12y ago
  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.
- dmd 12y ago
  $0.75 seems incredibly inexpensive to me. Modafinil, by comparison, can be $50 per dose.
  - xeroxmalf 12y ago
    Or even on the higher end, some MS drugs like Copaxone can be upwards of $200 to $300 per dose.
- thathonkey 12y ago
  $0.75 per pill is super cheap especially for a novel treatment. What are you talking about dude?
- evilduck 12y ago
  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.
coldpie 12y ago
Yep. On my insurance plan, I spend about $250 per month on Type I Diabetes supplies. That adds up.
- Shivetya 12y ago
  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.
- falsestprophet 12y ago
  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.
- georgef 12y ago
  It varies a lot, though. My T1D supplies (as a college student on my parents' insurance) cost more like $50-$75 a month.

andrewstuart 12y ago

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

thinkcomp 12y ago
This page gives a good summary as to why mice are used in research: http://research.jax.org/mousegenetics/advantages/advantages-of-mouse.html 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 12y ago
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
ars 12y ago
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.
cperciva 12y ago
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 http://en.wikipedia.org/wiki/Biobreeding_rat) or NOD mice (http://en.wikipedia.org/wiki/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 12y ago

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-against-diabetes/ 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.

xxs 12y ago
Yes beta cells killed by the immune system is Type I.
- nhstanley 12y ago
  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.
  - ars 12y ago
    Is type II treatable by lifestyle changes, or are the effects permanent once it occurs?
    - ratpik 12y ago
      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/ http://www.janacare.com/, we are using technology to help this process.
  - pdoconnell 12y ago

agumonkey 12y ago

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

orofino 12y ago

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

deleted 12y ago
[deleted]
- nwndarkness 12y ago
  This article is related to curing Type 1 diabetes which has nothing to do with obesity.
gabemart 12y ago
The website WIAT.com is for the radio station WIAT 42 based out of Birmingham, Alabama.

ars 12y ago

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.

cperciva 12y ago
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.
zaroth 12y ago
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 12y ago
  > 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 12y ago
    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

bitL 12y ago

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 12y ago
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.

hospes 12y ago

Since this drug was used since 1982, I wonder if it is necessary to start human clinical tests. They can first analyze data on people with diabetes who have been taking this medicine for high blood pressure.

micro_cam 12y ago

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-regenerating-mouse/ http://singularityhub.com/2010/05/11/the-incredible-regenera...

bayesianhorse 12y ago

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.