The cure that I’m betting on is the CNIP (Cellular Networking Integration and Processing) model in the works at Syner-III. It involves reprogramming some the patient’s non insulin secreting pancreatic cells to produce insulin. There are no exogenous cells introduced so no immune response.
They are currently planning the animal trials, and are looking at starting human trials within about 3 years.
This is really neat!
This monograph explains the problems associated with stem cell implants and single phase DNA cellular reprogramming in the liver, and how CNIP obviates these problems. It’s fairly technical, but FUD’ers should have no problem understanding it.
(You have to download this PDF to read it)
@docslotnick reported on this fascinating project in this thread in the past:
Here is an interesting 2016 NIH article from Curr. Pharm. Biotechnol. about the project:
I’ll have to read this when I get home. My work computer says your link is dangerous 
These are my quick thoughts on the original post:
I think it is a bad idea to “place bets” (that is, to put your emotional backing behind one particular line of research). I prefer to “play the field”. There is nothing to be gained by “betting on” one piece of research. Better to cheer for all of them. After all, it doesn’t really matter which cure is successful, just that one is.
I blog on research which is in human trials (ie. “clinical trials”), so I won’t be blogging on this until it enters human trials (unless something unusual happens).
I previously blogged on research when the researchers announced that they were going to start human trials within 2 years. However, I stopped doing that, because I found that many of the trials promised in 2 years never actually materialized. Now I wait for the actual start.
My biggest worry with research of this general type, is that the body’s immune system will destroy the newly created beta cell in the same way it destroyed the previous beta cells. This research works be encouraging alpha cells to transition into beta cells, but if the immune system destroys those new beta cells, what’s the point?
Large animals do not get type-1 (“autoimmune”) diabetes. (They can get type-2 diabetes.) Therefore no amount of large animal testing is going to address the autoimmune issue that worries me. This testing is still important, because of safety issues; they are giving a genetically engineered virus and that requires safety testing. But these tests will not give an effectiveness signal which would reassure me. (Large animals can have their beta cells killed off with a toxin. This creates a healthy animal without beta cells, but that’s not a type-1 animal. Such animals are good for testing pumps and CGMs, but not immunology based cures.)
I’m sorry to be such a downer. When (if) this enters clinical trials I’ll report on it, and cheer for it. I cheer for all research. But don’t overlook the weaknesses of whatever research you are focusing on.
Joshua Levy
@joshualevy Couple of points I think you mischaracterized concerning this research
They are NOT turning Alpha cells into Beta cells. Specifically, the point of CNIP is to give Alpha cells the ability to secrete insulin in a glucoregulated manner. They will still be Alpha cells. No new exogenous cells are being utilized. These Alpha cells are the host’s cells that have not been destroyed by their immune system.
The virus vector being employed is an FDA approved procedure currently in use. Of course it has never been employed with the CNIP cocktail, so there certainly is the small chance that it will not be safe.
They specifically address this point in their original study. They are not using toxins to destroy the test animal’s beta cells. They are reducing the beta cells via partial pancreatectomy, and taking action to not have the remaining beta cells proliferate.
You are certainly correct that one should not become emotionally invested in any single study for a cure. But when a novel method that makes so much sense and has had such preliminary success is announced, it certainly is a cause for excitement.
I’m doubtful that the difference between “Beta cell” and “Alpha cells that secrete insulin in a glucoregulated manner” is that big a difference. We know that one autoimmune target is insulin, so that one is likely to target the new alpha cells, because they generate insulin. But what about the autoimmunity that targets GAD or ZnT8, or IA-2A? The insulin producing alpha cells may well attract these autoantibodies. This is exactly why testing on people or animals with immune diabetes is important.
My understanding is that the virus vector is customized for each treatment. The base virus they are starting with has been used before, but the exact virus injected is specific to this treatment.
I’m sorry I did not absorb that detail from their research, but I don’t think it matters at all.
Exactly how they are killing/disabling the pancreas is not important. Those animals do not have the immune system flaw that people with type-1 diabetes have, and that is important because type-1 is an immune system disease. And their complexity in removing part of the pancreas, but not all, and preventing the remaining beta cells from proliferating, does not help. Those pancreases in the experimental animals are quite different than pancreases in people with type-1 diabetes.
Now in a certain sense, maybe none of this matters. Personally, I pay attention to research when it is done on people, not animals. So I’ll be waiting until they have good results in people before getting excited. While I think their big-animal research is particularly bad at showing efficiency, it is certainly required to show safety, so they have to do it. I would just be very careful about interpreting success in those animals as signalling future success in people.
Joshua
I just took a quick skim of the 2016 paper linked to near the top of this thread. (I’m sorry I don’t have time to read the whole thing.) But as far as I can see, their mouse testing was done on “generic” mice. That is, standard laboratory mice, and not NOD mice (which have a form of immune type-1 diabetes). The mice they used had a “partial pancreatectomy” (I assume the procedure you describe for the big-animals.) This means their mice research had the same problem that I’m worried about in their big-animal research, but in mice, there is no reason to have this problem. We have mice that have autoimmune type-1 diabetes. (In big-animals, we do not.)
In my humble opinion, this is a serious weakness. If you (or anyone) talks to these researchers, you might want to ask them why they did not use NOD mice, which seems like a much more logical choice.
I know that many people think that NOD mice are a poor model of humans with type-1 diabetes (because successes in those mice have not led to successes in people), but I don’t think there is any doubt that it is the best model available. I do not understand why someone would use a worse model in mice, when a better one is available. (Even if the better one is not that good.) Surely the price difference for different types of mice is too small to worry about?
Joshua
I am guessing the reason they didn’t us NOD mice, is simply they are trying to see if the cellular therapy can work, the 2nd step would be NOD mice or another animal model, then they would eventually get to humans if it continues to work.
If you used NOD mice in step one, you wouldn’t know if the modification was working if the mouses immune system killed the pancreas cells quickly. Also, if this technique doesn’t work for diabetes, they would still have good information about what does work as they pivot.