Type 1 Diabetes Cured in Dogs

Type 1 and LADA
1

Hey guys, most of you probably don't know me since I haven't been on here in a few years, but I saw this article and I just had to come back and share it with you.

http://medicalxpress.com/news/2013-02-spanish-diabetes-dogs.html

A team of Spanish researchers managed to cure Type 1 Diabetes in dogs. Four years later they have remained normoglycemic and the treatment was extremely "simple." That's the very short version, but you should read the article for more.

This has made me pretty excited and hopeful that human trials will start soon.

2

I hope so. Diabetes gets on my nerves.
With that said I do believe the first trials for insulin began on dogs as well.
Hopefully this will be a trend. :)

3

Thanks for the link. Studies like this are very exciting and hopefully will provide a piece of the puzzle in curing Type 1.

4

hee hee hee!

5

Raining on the parade, I don't think I'd place much weight on this research. The viral vector for introducing glucose sensing/insulin production capabilities into muscle cells *is* interesting, but there's a core thing that's being left out here.

This wasn't autoimmune type 1 diabetes; it's closer to what pancreatitis can lead to (namely, destruction of the cells via non-immune vector). Specifically, they waxed the islet cells via a chemical cocktail. Studies like this have been done before- in those cases, you can transplant islet cells back into the body and as long as they immediately take (requiring either immunosuppressants if they're foreign, or trickery like dumping the cells in the liver to avoid the immune system, or host compatible via derivation from stem cell) a 'cure' *is* doable, and has been done before. Props for them doing it via an interesting new vector.

That said, you try this on a autoimmune type1 and the immune system is still going to destroy those cells- keep in mind most studies show we actually *do* produce those cells still, the immune system however kills it off. I'm having a helluva time tracking down the raw research paper, but the interpretations I've seen have kind of confirmed the view here- http://www.nlm.nih.gov/medlineplus/news/fullstory_134024.html for example. This sort of therapy seems more suitable for type2- insufficent production (or increased resistance), assuming it could be translated to humans (which seems to be a bit of a 'no' unfortunately).

On the upshot, http://faustmanlab.org/clinicaltrial/clinicalt.html I wound up finding and that's rather interesting; basically immunomodulation, kicks the immune reaction against islet cells in the junk. The trials haven't lead to long term cures- the modulation wears off- but from my standpoint, it's on the right track (for reference, her lab keeps popping up in the news every few years; first curing mice, then the most recent trials where autoimmune type1s were able to go off insulin for a good chunk of time). Worth flipping through http://faustmanlab.org/docs/newsletters/DrFaustmanUpdate_1112d-web.pdf if you've got interest.

6

Is it really true that the autoimmune cells will kill any cell that makes insulin and not just beta cells? So it is the insulin-producing nature of a cell that gets attacked somehow, not some quality of the cells that normally make insulin? I haven't read much about the science of the actual autoimmune attack -- what is it that the immune cells are zoning in on or recognizing? I had always pictured some kind of receptor on the beta cell surface, but I don't have much of a biology background.

My first thought when I read this is that it might cause some seriously misshapen thighs. I'd do it anyway, though, in a heartbeat.

ETA: For some reason I kinda didn't buy the article you linked about the dogs study. The scientists poo pooing it were just not very convincing.

7

I think ferringb is wrong. Actually the trick to reprogram the muscle cells is dangerous but efficient. The muscles cells will still have the signature of muscle cells - even if they produce insulin. Thus the immune system will not attack them. Whether this virus based vector approach is safe or not is another question. I highly doubt that any ethics commission will allow trials with humans for the 10 years. Once the DNA of these cells has been altered there is no way back with all the possible consequences.

8

You may have me on that one actually, although as far as I know there's multiple antigens involved: insulin, GAD, and islet (I've not found any research as to what the specific characteristic they go after- if you find out, I'd be curious). Those are the core three I know of; it's worth noting that the point I raised also was raised by a few doctors in the referenced article (email 'em; might get a response where they clarify their views, or your question as to the antigen).

The closest paper I'm finding at this hour (fricking 5am my time) is their previous experiments w/ mice: http://diabetes.diabetesjournals.org/content/55/6/1546.full . If you find the dog paper, I'd be curious. The thing that's a bit weird there is a viral vector to induce an immune response for mice, *has* been accomplished before- rather than the cocktail (http://en.wikipedia.org/wiki/Streptozotocin) route they used. Presume they did the cocktail for control reasons, and since it's a helluva lot simpler.

Either way, the immune component of type1 isn't there in there experiment; as said, this is more like pancreatis induced type1. Doesn't mean that the research is crap, it just means that the immune interaction there is currently unknown

Re: the 'poo pooing'; keep in mind this is the NIH. Not to say they're perfect, but they're probably more trustworthy then some random jack ass on the internet- say me for example :) . I will say, their comments re: the speed of response to changing BG should be a concern that makes sense- the pancreas basically can dump it straight into the mainline of the body, muscles would have to effectively bleed it out meaning increased delays in addition to the sensing component potentially being delayed.

Either way, in my view, it's an interesting technique- but they've not tried it on a proper diabetic yet, just a disease model. Having it behave correctly despite a belligerent immune system would carry a lot of weight from my view.

That said, I still prefer the notion of just plain fixing the immune system mistargeting- hence the Faustman links. I'd strongly prefer to have my immune systems misbehaviour corrected- and pancreatic islet cell regeneration that occurs (hopefully to normal/full levels, although I've seen no studies that way)- rather than have a muscle mass converted into a quasi cgm/pump. Basically fix the cause, rather than go quasi artificial.

Cheers-

PS: In re-reading this, that's probably some of the worst english I've written yet. I blame the hour; pardon the wordiness. :/

9

So, you mean, once the cells are altered, we don't have any way to undo it or get rid of them? I feel like there should be a way that's not beyond our means. Like, if we can mark and then target cancer cells to kill them (which I think we can do, can't we?), why can we add some piece of DNA in these vectors that will mark the cells in a way that will enable us to target them later if they go rogue or something?

I do agree, though, that it's a little unsettling to be messing with the DNA in our cells. Are there any other similar models that we already do?

10

The tone of that article strikes me as weird even if it is the NIH. Like this:

Trucco said he doesn't believe this therapy could translate to humans.

"Human beings are not clones of dogs. Beta cells are more complicated than muscle cells. Muscles just can't secrete insulin quickly and efficiently like beta cells do," he said.

It's such a cursory statement, especially since it is a response to a paper in which scientists are reporting that muscle cells, in fact, were able to secrete insulin quickly enough and efficiently enough to keep the dogs' blood sugar stable.

And as far as fixing the immune system being a better way to go... I'm not going to be picky about which way I'm cured unless it comes down to the worms, in which case I will have to go on some kind of anti-anxiety meds to get the worms down or maybe be hypnotized or something. Otherwise, if I'm cured, I don't think I'm gonna have much in the way of mixed feelings about it.

I do feel like we read about something that seems SO PROMISING every now and then but then I never hear reports that the research is actually progressing. Maybe the tb vax thing is progressing a bit, but every time I check it looks the same to me. And with that one, I'm afraid they'll start using it on patients in another twenty years when I'm 40 years in and have terrible complications and my body is incapable of growing new beta cells. No matter what none of these things is going to be available tomorrow, but at least with this DNA therapy, it is not obvious why someone far along and/or old couldn't benefit.

11

One site I like, by Joshua Levy, that reviews research on cures to T1D is: http://cureresearch4type1diabetes.blogspot.com/

He is cautious with how he analyzes and reports on diabetes research. His site is not exhaustive, but does cover current American trials I believe.

12

Thanks for that link! Lots of interesting information there!

And I found out that I am in remission! lmao (if only) Here's what he says (this is a quote from Levy's blog, not sure how I'm supposed to document that?):

A Note About "Remission"

Some type-1 researchers use the term "remission". Specifically, they use it to mean "Uses less than 1/2 a unit of insulin per kg of body weight per day". Don't be confused. Non-researchers think of "remission" as meaning "doesn't use insulin", but that is NOT how researchers use the term. If your child weighs 40 kg (about 88 pounds), and uses 20 units of insulin, or less, then they are "in remission", and this does happen to some people during the honeymoon.

I'm tickled that I fit the definition (although I wouldn't if I ate a piece of chocolate cake or lost a few more pounds), but I gotta say that even under 20 units a day it's no great shakes.

13

There is a huge gap in that article I just read it.
It makes it seem like one injection and the animals were magically cured.
I mean Beta cells would take a while to grow at least wouldn't they? there is no mention of how the genes fix the problem. It never says they dogs regrew normal levels of islet cells. It is not mentioned at all what is actually supposed to have happened.
It is kind of weird that it is left out. It almost sounds like a cure for type 2 except that they mention type 1. Still the description does not sound like type 1.. It is very odd

14

I don't think the dogs ever grow beta cells or islets. I believe that the
DNA is taken up by the muscle cells themselves and they just start churning out the proteins that are coded in that DNA, one being insulin. Does that make sense, or do you still see holes?