Could this be a game changer?

[Chris24Main]

Agree, that's a different discussion.
My issue was with the statement that it would be worrisome if T1's ate exactly as non T1's with this perfect insulin, only because they have T1.

Totally understand - was not implying that at all. @Melgar has the sense of it. Backing off though...

 

[Tokolosh]

Everyone is different, difference in how we manage either T1 or T2, IR, Exercise, Eating and how our individual bodies react to all of this. For T1's we all differ in how various Insulins work and therefore use various types of Insulin. We will all react differently when diagnosed with T1 or T2 and will all react differently when, if we are lucky, break free of Diabetes. All very good subjects but essentially not really for this particular subject.

Getting back on the Subject.

The article explains that this Smart Insulin is in the early stages of Research, albeit it has been going for some time now. It was focused more on the Funding of the Research currently happening. We all know Research is a very costly activity especially when it comes to medical, most times research creates different branches to follow and will divert the subject down those. Scientific research has advanced significantly over the years and now, with new developments of experimental equipment, chemistry knowledge and may I suggest AI, research can develop much quicker. You only have to look at how quickly they developed the Corona Virus vaccines to realise this. Might be controversial but I believe when they do get to the testing on humans part of this new Smart Insulin, there will have been many questions during the research and each will be checked, tested and evolved to make sure it is safe for humans. I don't know if I will be around when it does become available for use but if came out today, I would certainly put my hand up for testing it on.

Going slightly off the subject of the Smart Insulin, although I think closely linked.

A more controversial part of research in this, is the research into Stem Cell creation of the Beta Cells. Hopefully, the fact that they have now developed a synthetic stem cell the controversy is now nullified. Not a scientist here lol so might be very wrong, but if, in Type 1, our Beta Cells are being destroyed by our immune system, they maybe able to change the genetics of our Beta Cells to prevent the immune system from reacting and destroying them.

Sorry if this is off Topic and if people are not happy with it, maybe we can create a different Forum Topic

 

[Ushthetaff]

I’m always quite wary when non diabetics class something as a game changer , there are lots of things which work in theory and on rats or whatever , but on individual diabetics I am a tad sceptical , but that’s me billy raincloud , I hope it works I really do but I’ll not hold my breath .

 

[Jasmin2000]

Going slightly off the subject of the Smart Insulin, although I think closely linked.

A more controversial part of research in this, is the research into Stem Cell creation of the Beta Cells. Hopefully, the fact that they have now developed a synthetic stem cell the controversy is now nullified. Not a scientist here lol so might be very wrong, but if, in Type 1, our Beta Cells are being destroyed by our immune system, they maybe able to change the genetics of our Beta Cells to prevent the immune system from reacting and destroying them.

Not quite - when you implant foreign (non-self) cells into the body you get an immune rejection. This is caused by recognition molecules on all cells (HLAs, Rhesus factors, etc.) which the immune system uses to identify invaders. There are companies making stem cells without these recognition molecules (such as SANA Therapeutics) and then the stem cells can be used to create beta-cells that won't be recognised as foreign (hypoallergenic cells).

But that's only half the story as in Type 1s the immune system destroyed the beta-cells even though they were "self" cells by mis-recognising normal beta-cell proteins as foreign. These immune cells will still be there are will still attack the new hypoallergenic beta-cells. And you can't remove the "immunogenic" beta-cell proteins as the cells would no longer be beta-cells.

Current thoughts are to encapsulate the cells in a coating (Vertex Pharmaceuticals) to prevent immune cells getting through - problem then is that insulin and antibodies are proteins and you can't get insulin out without antibodies getting in.

There are ways to remove the autoimmune cells that originally destroyed the beta-cells, e.g. by bone marrow transplant. But that brings huge risks to patients and I'm not sure regulators would accept the inevitable death rates compared to success rates. Much more likely is CAR-T therapy where your own T cells are tuned to destroy those autoimmune cells. I have no doubt that this will be done soon but it's darned expensive and regulators are unlikely to approve it for most T1s who are not in life threatening danger.

 

[Jaylee]

I’m always quite wary when non diabetics class something as a game changer , there are lots of things which work in theory and on rats or whatever , but on individual diabetics I am a tad sceptical , but that’s me billy raincloud , I hope it works I really do but I’ll not hold my breath .

I wouldn’t disagree with you..

The stuff I used to read in “new scientist” publication in the 1980s.

 

[Tokolosh]

Not quite - when you implant foreign (non-self) cells into the body you get an immune rejection. This is caused by recognition molecules on all cells (HLAs, Rhesus factors, etc.) which the immune system uses to identify invaders. There are companies making stem cells without these recognition molecules (such as SANA Therapeutics) and then the stem cells can be used to create beta-cells that won't be recognised as foreign (hypoallergenic cells).

But that's only half the story as in Type 1s the immune system destroyed the beta-cells even though they were "self" cells by mis-recognising normal beta-cell proteins as foreign. These immune cells will still be there are will still attack the new hypoallergenic beta-cells. And you can't remove the "immunogenic" beta-cell proteins as the cells would no longer be beta-cells.

Current thoughts are to encapsulate the cells in a coating (Vertex Pharmaceuticals) to prevent immune cells getting through - problem then is that insulin and antibodies are proteins and you can't get insulin out without antibodies getting in.

There are ways to remove the autoimmune cells that originally destroyed the beta-cells, e.g. by bone marrow transplant. But that brings huge risks to patients and I'm not sure regulators would accept the inevitable death rates compared to success rates. Much more likely is CAR-T therapy where your T-own T cells are tuned to destroy those autoimmune cells. I have no doubt that this will be done soon but it's darned expensive and regulators are unlikely to approve it for most T1s who are not in life threatening danger.

Yes I read all that when I was looking it up. Was just my short summary to a rather large subject. I'm just hoping that they can get round the issues of the autoimmune nature of the disease. I believe they are getting closer to achieving this but there is the issues you pointed out. I believe there have been different trials conducted by various labs and the results seem promising so far.

 

[Jasmin2000]

Yes I read all that when I was looking it up. Was just my short summary to a rather large subject. I'm just hoping that they can get round the issues of the autoimmune nature of the disease. I believe they are getting closer to achieving this but there is the issues you pointed out. I believe there have been different trials conducted by various labs and the results seem promising so far.

Some info on trials: there have been clinical studies for encapsulated stem-cell derived beta-cells (mostly from Viacyte, now Vertex, going back 10 years or more) but not the hypoallergenic beta-cells as these haven't been generated yet. There haven't been any trials with autoimmune suppression in the context of stem-cell derived beta-cell transplants as they haven't been made yet.

So IMO the first "launch" of any product will be the encapsulated cells in conjunction with immunosuppressive drugs for life-threatening diabetic situations, A more general solution for T1 is 10-15 years away, but with a high likelihood of success.

 

[Jaylee]

Totally understand - was not implying that at all. @Melgar has the sense of it. Backing off though...

Don’t be dissuaded.

This is a forum.

Theoretically. I see this idea more like a “smart basal” for non-pumpers, more than something that can handle “pizza.” Or a Jaffa cake.

 

[Jasmin2000]

Theoretically. I see this idea more like a “smart basal” for non-pumpers, more than something that can handle “pizza.” Or a Jaffa cake.

But for that you'd be better off with a very fast-acting insulin that you can jab when you're eating. A smart insulin is supposed to hang around like a basal but be inactive until you trigger it - the downside is you can trigger it with non-carb spikes from exercise, stress, shock, other hormonal spikes, etc. It would be a time-bomb and we'd all be walking around with pockets full of Skittles. (note to self - buy shares in Skittles)

 

[Antje77]

the downside is you can trigger it with non-carb spikes from exercise, stress, shock, other hormonal spikes, etc.

Why would that be a downside?
As it is, I inject for things like vigorous exercise, stress from dentist and endo visits, foot on the floor effect, monthly changes in hormones. All those spikes are from my liver dumping glucose, for me it doesn't matter if glucose comes from food or my liver, it needs insulin to be dealt with anyway.

 

[Jasmin2000]

Why would that be a downside?
As it is, I inject for things like vigorous exercise, stress from dentist and endo visits, foot on the floor effect, monthly changes in hormones. All those spikes are from my liver dumping glucose, for me it doesn't matter if glucose comes from food or my liver, it needs insulin to be dealt with anyway.

You're injecting a known amount for a known effect. Current smart insulin design cannot dose like you can. It assumes that each circulating inactive insulin molecule will bind a certain number of glucose molecules (say 20) to become active (glucose sensing effect). However, in a population of insulin molecules some will bind no glucose, some bind 20, and all the numbers in between to produce a population loaded with 0-20 glucoses.

The full ones are now active, but others require a few more or many more glucoses to become active. The problem is you have no idea how much of the remaining inactive insulin will be active with the next spike - or how much of the glucose from the last spike is still floating around bound to inactive insulin. Makes my head hurt.

I'm not surprised this problem has defeated scientists for the last decade - the pancreas doesn't secrete smart insulins - it does the brainwork itself. Nevertheless, solving this population dynamics version of Fermat's theorum would be of benefit to drug delivery in a huge number of other chronic diseases.

 

[Antje77]

You're injecting a known amount for a known effect.

That sounds much better than winging it, which is definitely what I do for liver dumps!

 

[Hopeful34]

You're injecting a known amount for a known effect.

Foot on the floor raises my blood sugar by nothing or by a different seemingly random amount each morning, as does stress etc, so I may know the amount I'm injecting (or my pump is giving me), but for a known effect mmh no.

Before I got a HCL pump I was definitely winging it as well @Antje77 As you and I (and others) have previously said in another thread, our basal requirements vary a great deal from day to day as well.

 

[jaywak]

Whatever , this is progress in the right direction and that has got to be good for everyone .

 

[Jaylee]

But for that you'd be better off with a very fast-acting insulin that you can jab when you're eating. A smart insulin is supposed to hang around like a basal but be inactive until you trigger it - the downside is you can trigger it with non-carb spikes from exercise, stress, shock, other hormonal spikes, etc. It would be a time-bomb and we'd all be walking around with pockets full of Skittles. (note to self - buy shares in Skittles)

I get that already with Lantus… it even still seems to work on gig nights long after it’s meant to have tailed of & depleted?
Which is rather strange.

But seriously,
I thought they had this proposed GRI as a “one stop shop” removing the need for traditional MDI?
Isn’t it also meant to (in theory.) “suspend” itself if BGs drop too low?

 

[Jasmin2000]

But seriously,
I thought they had this proposed GRI as a “one stop shop” removing the need for traditional MDI?
Isn’t it also meant to (in theory.) “suspend” itself if BGs drop too low?

That's the theory - the hurdle in development is how to "suspend" an insulin that is always present and is activated by glucose, when we all have some glucose in our blood. How can you prevent all of the suspended insulin from becoming active?

If it were simply the presence of glucose that activates the GRI then it wouldn't stop until your BG were close to zero. The only solution is to engineer the protein to have a high on/off rate of glucose binding at the activation site, so that it somehow only activates at a certain glucose concentration, say 6.5 mmol/L. Easier said than done.

 

[Jaylee]

That's the theory - the hurdle in development is how to "suspend" an insulin that is always present and is activated by glucose, when we all have some glucose in our blood. How can you prevent all of the suspended insulin from becoming active?

If it were simply the presence of glucose that activates the GRI then it wouldn't stop until your BG were close to zero. The only solution is to engineer the protein to have a high on/off rate of glucose binding at the activation site, so that it somehow only activates at a certain glucose concentration, say 6.5 mmol/L. Easier said than done.

This is moving into the realms of sci-fi.
But having a sensor tell the GRI to “cease & desist” if going low is one idea?
But that’s got to be walking into theoretical “nano tech” territory?

 

[Jasmin2000]

This is moving into the realms of sci-fi.
But having a sensor tell the GRI to “cease & desist” if going low is one idea?
But that’s got to be walking into theoretical “nano tech” territory?

Hey, it's all sci-fi until it's not! When I got my first BG meter, sci-fi was the CGM, but here we are.

You hit the nail on the head with the definition of the problem - a sensor to switch off the GRI at low BGs. But we don't need Borg nanoprobes (hi ST fans!) as we already have the sensor (CGM) and we have fast-acting insulin. In effect the closed loop system does what a GRI is supposed to do - the only difference is convenience.

There is another system that has a perfect sensor and perfect insulin deployment functions - the beta-cell and that's why I favor the lower hurdles of stem-cell derived beta-cell transplants.

 

[Jaylee]

Hey, it's all sci-fi until it's not! When I got my first BG meter, sci-fi was the CGM, but here we are.

You hit the nail on the head with the definition of the problem - a sensor to switch off the GRI at low BGs. But we don't need Borg nanoprobes (hi ST fans!) as we already have the sensor (CGM) and we have fast-acting insulin. In effect the closed loop system does what a GRI is supposed to do - the only difference is convenience.

There is another system that has a perfect sensor and perfect insulin deployment functions - the beta-cell and that's why I favor the lower hurdles of stem-cell derived beta-cell transplants.

I know that feeling with the first meter. In comparison to pee testing. It was so civilised.

I feel the way forward is the stem cell research & advancement.
I remember pre internet tracking down & phoning a lab after a breakthrough I read about in “new scientist.” I was up for being a guinea pig…
Probably I little naive at the time. It ended with me getting “stone walled.”

Till then, HCL is probably the “closest” we got? But that’s another stone wall for me…

 

[Libby66]

That's sounds fantastic , I will pray that it happens soon .

Me too