Diabetes research
Shemeska
Adventurer
Color me underwhelmed.
She's still going to be on immune suppressants for the rest of her life. A true cure for diabetes is going to require 2 things:
1) Suppression of the abberant T cell mediated autoimmune attack on mature islet cells, or the destruction of those cells specific to the response.
2) Replacement of the islets.
Most research that gets to the press or is lauded by the major diabetes groups are a false hope since they don't do a thing to solve the 1st issue above. Anti rejection drugs have problems in and of themselves, and the long term survival rate for transplanted islets isn't all that good.
There has been some work in the past 4 years or so trying to solve the immune issue entirely. Experiments, first published in the journal Science, by Faustman et al have demonstrated that TNF alpha at certain concentrations causes active T cells in mice, aka those involved in the destruction of islet cells constantly, to undergo apoptosis. Not only that, but they also found that the mice regained normal blood sugar levels shortly after that. Further investigation found that the islets were regenerating via precursor cells from the spleen, and that this was constant even in late stage diabetics in which there were no active islet cells at the start of treatment with TNFa.
The mice they've used have their diabetes caused by the exact same T cell autoimmune response that is present in humans, making them a very effective model for the disease. Also, there's now published evidence to suggest that human islets also are derived from spleenocyte precursors. End result being if you shut off the immune response in type one diabetics you could end disease.
Other experiments have worked in mice using spleenocytes from other mice to ameliorate the immune response in the diabetic animals.
Faustman has been approved for stage 1 clinical trials in humans of, last I checked, one off patent drug that induces TNFa production by the body. I've got my fingers crossed.
Other recent research has involved a paper to be published in the journal Gastroenterology. Researchers working to create beta islet cells from a line of adult stem cells applied the same growth factors to unsorted leukocytes (human). They injected the cells into diabetic mice and found that the animals blood sugar levels normalized for a period of time before their immune systems rejected the human cells. Apparently the white cells had been prompted into producing insulin in response to high blood sugar levels. This is interesting since I wouldn't have suspected it, and the induced cells might not be recognized by the T cells that otherwise destroy islet cells. I'd also worry about how it might affect certain type of white cells (ie immature B cells, memory cells, plasma cells) over a long period of time.
She's still going to be on immune suppressants for the rest of her life. A true cure for diabetes is going to require 2 things:
1) Suppression of the abberant T cell mediated autoimmune attack on mature islet cells, or the destruction of those cells specific to the response.
2) Replacement of the islets.
Most research that gets to the press or is lauded by the major diabetes groups are a false hope since they don't do a thing to solve the 1st issue above. Anti rejection drugs have problems in and of themselves, and the long term survival rate for transplanted islets isn't all that good.
There has been some work in the past 4 years or so trying to solve the immune issue entirely. Experiments, first published in the journal Science, by Faustman et al have demonstrated that TNF alpha at certain concentrations causes active T cells in mice, aka those involved in the destruction of islet cells constantly, to undergo apoptosis. Not only that, but they also found that the mice regained normal blood sugar levels shortly after that. Further investigation found that the islets were regenerating via precursor cells from the spleen, and that this was constant even in late stage diabetics in which there were no active islet cells at the start of treatment with TNFa.
The mice they've used have their diabetes caused by the exact same T cell autoimmune response that is present in humans, making them a very effective model for the disease. Also, there's now published evidence to suggest that human islets also are derived from spleenocyte precursors. End result being if you shut off the immune response in type one diabetics you could end disease.
Other experiments have worked in mice using spleenocytes from other mice to ameliorate the immune response in the diabetic animals.
Faustman has been approved for stage 1 clinical trials in humans of, last I checked, one off patent drug that induces TNFa production by the body. I've got my fingers crossed.
Other recent research has involved a paper to be published in the journal Gastroenterology. Researchers working to create beta islet cells from a line of adult stem cells applied the same growth factors to unsorted leukocytes (human). They injected the cells into diabetic mice and found that the animals blood sugar levels normalized for a period of time before their immune systems rejected the human cells. Apparently the white cells had been prompted into producing insulin in response to high blood sugar levels. This is interesting since I wouldn't have suspected it, and the induced cells might not be recognized by the T cells that otherwise destroy islet cells. I'd also worry about how it might affect certain type of white cells (ie immature B cells, memory cells, plasma cells) over a long period of time.
Torm
Explorer
Interesting.Shemeska said:
And I want to ask a question, but I'm a layman when it comes to biology, and I don't want to invoke the same sarcasm you just offered to an article obviously written by and for people "below your pay grade" when it comes to biology.Little pieces like this are written as human interest pieces to give people hope, not to inform scientists - they have more advanced journals for that, as you pointed out. Why you hatin'? And do you expect that attitude from people in other fields that know more about them than you do?....
Besides, if I wanted to fuss about something in that article, a clearer target was the annoying use of caps - which a writer or reporter should know something about. Ack!
Torm
Explorer
I'll go ahead and ask the question, anyway -
Based on what you just said, do you know if there is any data on what happens to Type I diabetics that get AIDS? Heck of a price to pay, I know, but does it cure the diabetes?
If so, I wonder if there is a way to use that. I read an article recently that talked about using a modified strand of HIV to fight cancer....
Based on what you just said, do you know if there is any data on what happens to Type I diabetics that get AIDS? Heck of a price to pay, I know, but does it cure the diabetes?
If so, I wonder if there is a way to use that. I read an article recently that talked about using a modified strand of HIV to fight cancer....
Torm, there is a subset of scientists -- and there's this subset in every discipline -- who prove there worth by knocking down what other people do. Its normal to see it in the newly educated. The less dry the ink, the more likely the attitude is.
After years of being at the bottom rung of a very tall ladder, it makes a lot of sense. I'm liable to have it happen to me in a few years if I don't stay aware of the possibility.
After years of being at the bottom rung of a very tall ladder, it makes a lot of sense. I'm liable to have it happen to me in a few years if I don't stay aware of the possibility.
Torm
Explorer
Eolin - I understand what you're saying. No offense, though, but don't help me.Eolin said:
I was trying to make what I consider to be a valid point, whereas you have gone on the attack a bit, yourself.And at this point, I'm honestly more concerned with hearing what people have to say about my question about AIDS and diabetes. I made my other point, and I'm done with it.
Turjan
Explorer
I think the point I'd criticize with this article is that it makes it sound as if the transplantation of islet cells was anything new. This has been done for many years now, with varying results. It's often not as efficient as a transplantation of a whole pancreas.
The risk of losing the transplant by an immune reaction is relatively high, as there are no easily visible markers available in this case. Usually, people who get a kidney transplant together with the pancreas or the islets, like many diabetics in a late stage, fare a bit better, because a kidney transplant shows fast signs of an attack by the immune system. Of course, this group of patients has much more severe problems, anyway, so that problems caused by immune suppression are usually seen as minor inconvenience.
I'm not a big fan of playing around with TNFα, as it's much too nonspecific and a central cytokine in lots of inflammatory pathways. The other experiment sounds promising, though.
The risk of losing the transplant by an immune reaction is relatively high, as there are no easily visible markers available in this case. Usually, people who get a kidney transplant together with the pancreas or the islets, like many diabetics in a late stage, fare a bit better, because a kidney transplant shows fast signs of an attack by the immune system. Of course, this group of patients has much more severe problems, anyway, so that problems caused by immune suppression are usually seen as minor inconvenience.
I'm not a big fan of playing around with TNFα, as it's much too nonspecific and a central cytokine in lots of inflammatory pathways. The other experiment sounds promising, though
.
Shemeska
Adventurer
Torm said:
1) It's nothing new.
2) I'm a type one diabetic myself, and have had the disease for 13 years. I'm growing rapidly jaded by the research approaches that are getting the most funding, and I'm tired of false hope that's wrapped up in the guise of anything but. Still, that said, I don't expect to be a diabetic 15 years from now.
And yes, TNFa is pretty damn nonspecific, but the same researchers have done some interesting work that seems to suggest that it's possible to reset a level of immune tolerance to transplanted islets derived from donor spleenocytes. However it has only happened in mice so far, though the earlier experiments in mice have worked with xenotransplanted human tissue as well. I'm keen on it to say the very least. The white cell experiments also have me very curious, both as a diabetic and as a cell biologist just to see what's actually going on. However I'd hate to cure the diabetes and end up with leukemia a few years later, so mucho safety testing needed even in the best case scenario of the cells producing insulin and sticking around in the human bloodstream.
And as for the diabetics with AIDS. Nothing has been published looking at it, but it's an interesting question. But it's a case of saving the city from a mongol horde by burning it to the ground. I'd rather have the diabetes than the HIV
But I'm not sure off the top of my head how large a subset of the T cells are involved in the autoimmune response against the islets, and following that, how much towards full blown AIDS you'd need to be before you ended up with the diabetes possibly reversing. Can't say for sure.
tarchon
First Post
I'm not even in that field, and I was thinking "this sounds like a pretty familiar old approach" I'm not sure they're written so much to give people hope as to get people to watch the news and generate publicity for the research. I don't object to reporting on research, but the term "breakthrough" gets blown around in these pieces a bit more than it ought to.Torm said:
And yeah, I think the rate at which optimistic "possible new treatment!" stories get tossed around for conditions like diabetes and AIDS would tend to jade a lot of people with the conditions.
I've heard the notion of HIV "treating" certain T-cell autoimmune conditions before, but I haven't seen any real research on it.
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