Former Biotech Scientist with T1D Explains Why Eledon’s Therapy Isn’t the Universal Cure

[00:00:00]Welcome to the Diabetes Nerd Podcast. My name is Ginger Vieiraa and I am your host. I've also lived with type 1 diabetes since 1999.

[00:00:09]We're doing something a little different this week. We're publishing two episodes because my interview with Dan Heler went on for 2 hours. We dug so deep into the immune system into the fact that there's actual multiple types of type 1 diabetes. And I don't even just mean type 1 and type 1.5. also known as LADA.

[00:00:31]I mean, Dan revealed that there's type 1 A and type one B. We're going to get into that. So, episode one with Dan is really or part one, if you will, is really all about the complexities of what a cure requires for type 1 diabetes. what we've already done to cure 1,500 people who've had eyelet cell transplants using very toxic amunosuppression drugs compared to Elodon's tego probart which is proving to be very low in toxicity and much safer and we're talking in this first episode about the complexities of the immune system that you don't just have immune cells that just fight. There's actually different types of activity in your immune system and different types of soldiers, if you will. Okay. In the second part of my interview with Dan, we dig into the FDA and what a clinical trial looks like to actually get the approval of a new drug and how complicated that is and how much time that takes and what it looks like if you develop something that works in one person, which they've done multiple times in multiple different types of therapies versus bringing it to a lot of people. So, buckle up. Dan is a super nerd. I try to keep up with just how intelligent this man is. He's lived with type 1 for over 50 years since 1973. And he's also a biotech scientist genius fella. So, here we go. The Diabetes Nerd podcast is proud to be sponsored by the Eversense 365day implantable continuous glucose monitor brought to you by Asencia Diabetes Care.

[00:02:27]I've been using the Eversense CGM since April of 2025 and I love it. It's the only CGM device that lasts a year. The sensor was placed just under the skin on my arm. The transmitter sits on my skin with this silicone adhesive and I can take it on and off. I love it. Learn more about Eversense 365 at eversensecgm.com.

[00:03:00][music] Welcome to the Diabetes Nerd Podcast. I am your host, Ginger Vieiraa. I have lived with type 1 diabetes since 1999, but my guest today has lived with type 1 diabetes since 1973. And if I'm a diabetes nerd, he is a diabetes super nerd. Super super nerd. All right, Dan.

[00:03:24]Dan, hello. Before I introduce you, hello. [laughter] >> Hello. Hello.

[00:03:28]>> Hello. Dan Heler, everybody. He was diagnosed. I I need to introduce you um because your your background is really important for the conversation that we're going to have. So um you were diagnosed at 10 years old in 1973.

[00:03:44]You are the co-founder and former CEO of Entra, which was a molecular diagnostics company. You led the development of handheld nano porebased diagnostic technology capable of single molecule detection. I don't know what that means, Dan, but I know it's extremely nerdy.

[00:04:03]Okay. [laughter] You guys raised you raised $25 million in venture funding.

[00:04:10]You collaborated with oncologists, major pharmaceutical companies, and the Gates Foundation on diagnostic technologies.

[00:04:16]You grew the company to more than 125 employees before it was acquired by a multi-billion dollar company. You also founded the Center for Entrepreneurship at the University of California in Santa Cruz, which helped launch university research into successful startups within the biotech industry. And we're going to talk about that. You The reason I I'm so grateful to have you come on is because I know you have extensive expertise in analyzing type 1 diabetes research.

[00:04:54]You have extensive expertise in the FDA regulatory pathway in biotechnology and medical device development and you are spending a lot of your time these days writing deep dive articles about type 1 diabetes research and all the cure therapies we're seeing come out. And you even um you you said on your Substack, so danheler.substack.com is where you can find all of this. You said, "I try to turn I spend my days looking at like this really boring, dense medical research and I try to turn it into content that most people can read, which I appreciate it."

[00:05:37]>> Right.

[00:05:38]>> Yeah.

[00:05:39]>> That that is my goal. That is hard to do, but that is my goal. [laughter] >> Yes. And I want to give a shout out to something you're just getting started with. We'll talk about it more, but you just started publishing your cartoons on Instagram under the handle T1D Humor.

[00:05:56]>> T1D humor. Yeah.

[00:05:58]>> Okay. Really fun cartoons, really beautiful artwork as well. Dan, we need to talk about the things that are really stirring up the type 1 diabetes community across the globe, which is Elodon's cure therapy and then just generally understanding what a cure for type 1 would look like, but also what's happening and what's been happening for decades. And you're going to help us clean up this mess because it's gotten very messy.

[00:06:28]It's gotten it's it's gotten messy and is about to get a lot messier. Um, but I think [laughter] the the the what I mean by that by messier is that what we're discovering are new realms and new domains that might allow us to move from where we've been into a new area. That new area is going to be messy. But but what it will mean is is that all the mess we've been dealing with will be a lot well just moves moves out of the way a lot of the things that we've been concerned about. And Eladon is a perfect uh story to tell that narrative about this transition from the old way we've been trying to cure diabetes to the newer coming ways. and and the transition that I'm going to talk about will make a lot more sense once I get started.

[00:07:25]>> Okay. And I know also can we just touch um briefly on your background and really you know obviously you're you founded a biotech company but the work you did at the University of California in Santa Cruz that gives you this insider knowledge of how this whole world of developing a drug a therapy works. Can you talk about that a little bit?

[00:07:50]>> Well, sure. And not just drugs and therapies, but diagnostics because they go hand in hand. So um you know having been a diabetic uh my whole life when uh when I was at UC Santa Cruz um I had started a lot of tech companies in the '9s and the UC system had a tech transfer model where university research uh researchers would file patents and then you license them to large companies. Typically that was the model.

[00:08:24]they didn't have a whole big strategy in starting new companies. So, I came to UC Santa Cruz where I got my uh degrees um in in AI, odd as it sounds, back in the 80s, but um the the goal was how can we do deep research into the patents that we filed, find a market for it, and who would license this? And so once we saw that connection, that's when we started promoting all these technologies to the pharma companies. So people who develop drugs would might want a molecule that's been developed or a technique to do something. So because they were so interested in our intellectual property IP, they would ring us in and be very honest about what they're doing. I've signed more NDAs than I can count.

[00:09:23]Right? So, there is no company we didn't somehow deal with. And they would be very honest. You know, our drug does this. We promote it as doing that, but here's our problem. And then they would say what their problem is and why they're telling us that is because we want to license your new technology in order to be able to do that. And so, you know, they would say, and they were, when I say honest, I'm talking, you know, we would not nothing illegal by any means, but just saying we emphasize these qualities, you know, when we talk to the FDA, we emphasize these things.

[00:10:02]We try to sell it as this is why it's beneficial for everyone, but we don't really talk about the problems with it. Not again, not illegally, but but it's that kind of thing that I learned about how we can help, right? It's it's marketing, it's positioning, it's when you when you talk to these when you talk to these executives, you know, they know exactly what they're doing. They they have a science background. They're MDs. They're PhDs. They're also business people. They understand how to characterize things and they leverage >> whatever the ecosystem is.

[00:10:43]>> Today's ecosystem is not what it was in 2011 or 12 or in or in the the whole decade that I was there. It was today it's what you're doing.

[00:10:55]>> It's media. It is social media. It is spreading wild that way. And how do they get into that? Sometimes they pay influencers. Sometimes they pay uh agencies or organizations to say position us in this way to help us because we're helping you, right? We are doing great things. Help us help you is is their strategy. So nothing nothing at all is nefarious, right?

[00:11:26]>> It's also not 100% of the story. So >> every I recently wrote an article about how the cure to diabetes won't there won't be one cure there will be many >> and there's the there's the the idea that we need to attack multiple things at the same time. So when we talk about Elodon what they've done is great but it's one thing it's one thing that's addressed but not other things. And sometimes that part of the message is lost.

[00:12:00]>> So again, not taking anything away.

[00:12:04]>> Yes, it's hard to explain. So this So what I hope to do here today is give some context about what's missing, >> what else is necessary to to get all this done and contextualize what they've done from, you know, and why is it better.

[00:12:21]>> Okay. All right. So tell me tell me what it takes to cure type 1 diabetes. I know you've got three three pillars, three factors here.

[00:12:31]>> Right. So let's let's first say what does it mean to cure diabetes? Well cure means there was something went wrong and you need to fix it, right? So, so to reverse autoimmunity, uh, most of us in T1 are familiar with the idea that it's autoimmunity that we something in our immune system kill our own beta cells.

[00:12:55]Whenever we talk to people who aren't diabetics, oh, my aunt is a diabetic and you know, and it's like, no, it's not the same thing, right? It's uh, we say our own beta cells. That's true, but it's not always true. So that difference is really hints at this new domain that I'm talking about that's newly being discovered in research. So to cure diabetes if you're going to do the autoimmune component it's genetic and there's technologies like crisper which people may have heard about gene editing where you somebody for example there's a lot of autoimmune diseases like let's think of cickle cell um where you know the your immune system is attacking you know certain things in the blood and and so forth so but it's a single nucleotide in your DNA So your DNA has CGAT. If one of them is wrong in a particular gene, it causes bad things to happen, right? And including type 1 diabetes. But you can change one gene and everything's right.

[00:14:04]Here's the thing to really be appreciate about autoimmune and diabetes is that there's a whole smattering thousands of different genes. And so the genes that are mostly affected are what's called the HLA, which is the immune system part of our gene. So it refers to the white blood cells that attack foreign bodies can somehow be, you know, changed to to attack our own cells. So, so the fact that there's so many different cells, what we call pathways to uh the immune response that causes autoimmunity.

[00:14:47]So, that's that's you know, to cure it, you'd have to cure that.

[00:14:51]>> We can't. That's just you just can't because there's too many genes. You don't know what to affect. And even if you did, >> you you could affect one thing and then cause another thing. So for example, when we're talking about immune suppression drugs like you know uh T-zield is trying to suspend the immune system from attacking so that you know stage one and stage two pre-type 1 diabetes it's delayed. Right?

[00:15:22]>> That's great. The problem is is it's also causing other autoimmune diseases in a small number of subjects. It's not being used very much. Not enough time has gone by, but that's what we're finding. The immune system is really persistent and it's just gonna try to figure out a way around all these things.

[00:15:42]>> And I want to I want to add for people, and I've explained this a lot before, but I think we need to keep saying it, that because a lot of people hear, well, that's not a real cure if I still have to take um medicine or if I have to get this transplant or whatever it is, that therapy that this company made, that's not a cure. I want the a cure that just fixes what's going wrong. I people really need to understand that's not possible because they can't turn off the immune attack yet and right they don't know how to do that. But also even if they did give you a pill that just got your immune system to behave. Most of us don't have any beta cells left to produce the insulin that we actually need.

[00:16:25]>> Exactly. So this is what now we call instead of we don't call it a cure anymore we call it a functional cure which we've redefined cure to mean being free from having to take insulin.

[00:16:37]>> Yeah.

[00:16:38]>> Okay. So if we can be free from that a lot of people consider that to be a cure. It's acceptable. So to do that you need three things. You need durability.

[00:16:51]new eyelets to replace the dead ones that no longer have. Durability, toxicity, so what are you taking to keep the immune system from killing those new eyelets that you put in?

[00:17:06]>> And then the supply you need >> to get a lot of eyelets, right?

[00:17:11]>> Um, so we can get a supply. I mean, you know, we all know that cadaavver eyelets is a supply capped thing, right? And we'll get more into that later, but the >> I'm just going to I'm going to lay in terms that I'm going to I'm going to take that down a notch and make it even simpler. So, you're saying that we need a supply an endless supply, which means somebody creating lots and lots of eyelet cells in a lab and eyelet cells contain beta cells. Beta cells produce insulin. You're saying we need some kind of toxicity, which sounds like a scary word. Why would we want that? But we need something that tells the immune system not to attack these amazing new cells that are replacing the cells that, you know, I certainly don't have and you certainly don't have any more of.

[00:17:56]Someone newly diagnosed might still have some um cells that produce insulin, but that attack goes on the longer that you've lived with type one. And then durability.

[00:18:06]Can you explain durability again? just that they last a long time.

[00:18:11]>> Okay. Yeah.

[00:18:12]>> Right. So your toxicity problem is we want to keep the immune system from doing these things but in the process we don't kill our liver [laughter] >> right or our kidneys and you know other kinds of things. So that's >> and that's people also like you can cure type 1 diabetes right now with a pancreas transplant a new kidney and boom wonderful you're making insulin.

[00:18:37]But guess what?

[00:18:39]>> Right.

[00:18:39]>> That's a really hard life and you now just deal with a whole bunch of other major health problems.

[00:18:45]>> Yeah, >> that's exactly right. Yeah.

[00:18:47]>> So, so, so those three things and we're going to talk about them. Um, but when we do, here's the thing that we need to un just keep in the back of your mind as I talked about all these things. The cure cannot be worse than the disease.

[00:19:05]M.

[00:19:05]>> So, no matter how much we hate T1D, the relentless grind and so forth, the fear that we're going to die early, all these things, no matter how much that can bother you, just having something that keeps you from having to take insulin is not necessarily better. Right. Right.

[00:19:22]>> You're still going to have to be compliant with a drug protocol. You're going to have to not be, you know, so we can get into all that later, but >> and yeah, >> I think that's >> Yeah. I mean, it's Alli Duggar is a perfect example of So, Alli's been on my podcast a few times. She had a pancreas kidney transplant, but she was at death's door.

[00:19:43]>> So, for her, >> um, because she very, as she's explained many times, she really barely took insulin for many, many years in in her teens and 20s. And so, for her, it was either a pancreas and kidney transplant or death. And she did nearly die several times. And so for her, the cure was better than the disease because she wasn't going to live much longer and now she does have a future. Right. So, >> right.

[00:20:08]>> Yeah.

[00:20:09]>> And there's a lot there's a lot of stories like that. And again, when I say the cure is worse than the disease, we also have to be very cognizant of people who are recently cured, right? And who just speak glowingly about, oh, my life is just so wonderful. This is one year, two years into it. It's this is not so this is why durability is such a key component to this and again we're going to get to all these things but >> can I ask you something really quick?

[00:20:40]Would the FDA approve a drug for use in humans that we've seen let's say 6 months to two years it's performing well this therapy combined with other drugs would the FDA approve that use in humans because it toxicity seems low seems non-existent maybe based on that it was given to monkeys for years and the monkeys did great >> well the FDA doesn't approve And I and there's a section that I'll get to at the very end is what exactly do these timelines look like? How long does it take for the FDA to approve something? And you know uh to you know sort of tease you a little bit. The FDA has already approved something that we're doing today that we talked today.

[00:21:29]you can be cured today if that's really uh what you want so long as you meet certain criteria that the FDA says, yeah, the cure has to be worse than the disease and your disease isn't bad enough.

[00:21:42]>> Right.

[00:21:42]>> Right. So, so these are the kinds of things. So, that's a foreshadow we'll get into. By the time we get there, >> you're going to already know so many things that you're just going to go, "Okay, I get it now. I understand."

[00:21:55]Right? All right. So, no, the FDA does not cure things based on its performance in monkeys. Right.

[00:22:00]>> Right. Exa. Exactly. Everything has to be done through human trials. You need to see that it lasts a long time.

[00:22:07]>> Yeah. And just because it lasts two years. Just because something lasted two years doesn't mean it's going to last 10 and therefore be worth an insurance company paying hundreds of thousands of dollars for you to receive this therapy.

[00:22:20]>> Well, that's true, but some people would just pay out of pocket to get it. I mean there are those >> very well off but that's not you know cost of course is a is an important consideration but the FDA's consideration is really you know as we we were talking about you would have to be eligible for I mean just look at it today we have all sorts of drugs that are just used today but nobody takes them because they're not eligible you're not allowed to take them now you can try to get it off market and stuff like that but So you see where this is going. So just because of some the FDA's approved something doesn't mean it's generally available. It means it's they put a fence around it to say well you have to have certain kinds of things.

[00:23:05]>> Yeah.

[00:23:06]>> Okay. So let's talk about durability.

[00:23:08]Okay. So a durability needs three things. Okay. The eyelet supply which we talked about. Now everybody remember beta cells is the part that died but our eyelets contain five cells and those include alpha cells which do glucagon and you know I'm not going to get into all that but just we have to understand that whenever we're talking about these things we're not talking about beta cells we're talking about eyelets and the reason why it's >> explain >> yeah I I mean I've explained to listeners on other episodes and please find it on my YouTube channel that those other cells produce five other hormones that are really important to support insulin and without them, you know, we struggle with a whole bunch of other things that nobody talks about.

[00:23:54]>> Go ahead. Sorry.

[00:23:55]>> Right. Okay. So, so, so anyway, we're always talking about eyelets. So, the supply of eyelids. Okay. Placement of eyelets. That's really important. The eyelet has to be in a place where the food comes in. you know, your blood, you know, the food comes in, the sugars around, you know, all these different hormones that are secreted besides just insulin >> that govern glommic control. So the the beta cells rely on signaling from these other things and all that requires the portal vein, which is the main vein that goes you eat food. that blood supply goes right to the liver, the pancreas, and all this stuff happens before it gets to the rest of the body. So if it So when we take insulin exogenously, I use an insulin pen. When it goes into the tissue or I'm sorry, the insulin pump works exactly the same way. It just goes subcutaneously. Now that insulin is going through your whole body before it gets to the liver.

[00:25:05]>> Yeah.

[00:25:05]>> And the liver is the supposed to be the first pass at insulin. And so why?

[00:25:14]Because it's a growth hormone. It helps produce all sorts of things. I'm not going to get into it, but the importance that it goes there first really helps glycemic control.

[00:25:24]>> And so people with type one managing insulin with I'm just going to reexplain that in another way. People with type one managing insulin given through our body fat subcutaneous we are missing out on this level of blood sugar management because our insulin is not directly provided to the liver first.

[00:25:45]>> This is true. But the other thing that we're missing out on is all the other hormonal signaling that happens. So when it comes to exercise, which is the most important thing a diabetic or a non-diabetic, I all humans need it, but especially us, exercise is the one thing that can really stabilize things, make things efficient and so forth. If insulin is not getting to where it needs to be first and it's just in our peripheral, it is so hard to manage.

[00:26:15]This is why hypoglycemia happens are are you know anyway you know all that >> and the alpha cell within the eyelet cell is we need that whole eyelet because you know for example one of those five cells the alpha cell works with the beta cell to prevent hypoglycemia.

[00:26:31]Um so >> that's right >> so we're getting poor delivery already with type one. Go ahead. I've had very deep conversations with people in the science community in T1D science and they say type 1 diabetes is really an alpha cell disease not a beta cell disease >> and it's true because remember the alpha cell is not dead it works the problem is it's dysfunctional it's disregulated so when we go hypo our alpha cell is just sitting there going I don't know what's going on because the beta cell normally signals the alpha cell to produce glucagon to keep right.

[00:27:10]>> So, and the other thing that alpha cells do is they produce glucagon when we don't need it.

[00:27:17]>> So, so when we eat and that portal vein gets it, it goes where does it hit?

[00:27:22]Alpha cell says, "Oh, I'm going to produce some glucagon now." But the >> beta cell which should be there is not telling it, "No, don't do that." Right?

[00:27:32]Or the delta cell is actually putting the brakes on. produce. We overproduce glucagon when we don't need it and we don't produce it when we actually really do need it because we don't have beta cells.

[00:27:42]>> We don't have the beta cells telling the alpha cells when to do their job and when to >> That's right. If you could regulate the alpha cell, >> the disease is so much easier.

[00:27:53]>> And there is a therapy coming around.

[00:27:56]Um, you know, they're in they're in their clinical trials still, but Zukara >> has that ZTO1, which will be interesting to see how that progresses.

[00:28:04]Yeah, the that would be great. I'm I'm aware of it and I'm, you know, I don't want to get too far off uh track. The problem is >> the fact that alpha cells still are there.

[00:28:17]>> You can't regulate them and what those drugs are trying to do with good intention is try to give you a glucagon when you need it, but it can't anyway.

[00:28:27]It's it's a tough problem to solve.

[00:28:30]But nevertheless, >> yeah. All right. Placement. We got placement.

[00:28:35]>> Placement of eyelets. So we have eyelet supply. Then the placement is really important. And then of course there's the immune system, right?

[00:28:45]>> So those three things keep keep all those in mind. So no technology has all three. So as we know eleon is just the immune response but it has nothing to do with eyelid supply and it has nothing to do with placement. Now we could solve eyelet supply and placement and eleon could be very great right but we don't have those two things solved yet but we're getting there. We're getting close. So okay >> so let's let's uh uh so all three of these things are in development simultaneously.

[00:29:19]Okay. So now here's where uh all three of these things but mostly the immunosuppression part. Let's talk about autoimmunity or let's just talk about the immune system. But >> let's just this is remember when I said that there's a smattering of genes that that are responsible for diabetes. The reason why there's a smattering is because there's a so many different genes that affect TE-C cells. TE-C cells are the soldiers that go out throughout your body, bind to things that shouldn't be there and kill them. Okay? So again, very complex, but they come in different forms. So e every single TE-C cell when it's made by the thymus, it's trained to identify specific kinds of things. to really reduce it down to simplicity for purposes of this conversation. They want to identify things that are foreign and they also are told to identify things that are just things whatever the thing is. It doesn't matter whether it's foreign or self but it's a thing. Okay.

[00:30:34]So a good example is cancer.

[00:30:37]>> We have tea cells that when you develop we develop cancer all the time all the time. And one, you know, you mentioned the company that I had. We had a diagnostic that could detect cancer.

[00:30:51]And the way we were able to do it is we just have these little probes that attach to the unique DNA of cancer. And we could see that it's there, right?

[00:31:02]Well, the immune system does the same thing. It catches cancer all the time.

[00:31:07]It's when cancer starts getting out of control that we can't stop it. That's the kind of cancer that we hear about.

[00:31:15]Well, what's interesting is is that a lot of the immunosuppressants would otherwise catch this cancer, but they've been suppressed.

[00:31:26]>> So, we're more susceptible to cancer.

[00:31:29]So, immunosuppressants have to target exactly what it is that they want to suppress. So there's cells that identify other and cells that identify self and cells that identify a thing. So a beta cell is a thing. It doesn't matter whether it's a cadaavver or stem cell or your own. It's a thing and that we have stem cells. So that's part of the autoimmunity that we cannot fix because there's too many genes involved.

[00:32:00]>> Okay? But we're going to try to hide from those and we'll get into that shortly. There's another kind of cell um that are uh called natural killers, NK.

[00:32:14]NK cells target things like uh well cancer. They also uh target um viruses.

[00:32:23]They they target all sorts of things that are just natural killers. It just said you shouldn't be here. I don't know what you are, but I'm going to get rid of you kind of thing. Okay, >> I'm really oversimplifying, but >> for where we're going. All of this is so important. So when I talk about things later, you're going to come back to this and go, "Ah, now now I understand." So >> killer cell tea cells, right? So the next thing that we have to understand and this is always been known but this is where the new research is going cells. These are like the generals for the soldiers. They don't just tell them they don't tell them what to attack.

[00:33:08]They tell them when and how hard. Is it really that intense that we need to kill right now?

[00:33:19][laughter] Right. So it's more like a thermostat.

[00:33:22]>> So if we now think of other autoimmune diseases, we know from just by knowing people that have them like people with Crohn's disease or cickle cell, all sorts of autoimmune diseases, it's not just a binary thing. They wax and they wayne.

[00:33:40]They go in and out. We don't know why, but they do. And type 1 autoimmunity has shown exactly the same behavior.

[00:33:51]>> Mhm.

[00:33:51]>> We don't just have the immune system killed our beta cells and that's it. You put in a new beta cell and now you need to suppress the immune system.

[00:34:00]>> Remember when I said in the very beginning in the very beginning of this I said not everybody has autoimmunity.

[00:34:06]>> There's a lot of people who do not have autoimmunity >> but they have >> right they have type ones. So the ADA has identified two different types of type 1 diabetes. Type 1 A is the autoimmune that most of us are familiar with. Type 1B is nonautoimmune. What they call idiopathic means which is we don't know. Now we don't know because we can't identify what killed it. But we do know from evidence that it happens. And the most common example that we're familiar with is molecular mimicry.

[00:34:49]Some virus, typically a virus, but it can be a lot of other things. Looks like a beta cell. So those teac cells that attack that virus, the general says, "Hey, there's a thing you need to kill.

[00:35:06]It looks like, you know, this virus.

[00:35:09]When did we see this last co? There was a huge up increase of type 1 diabetics in during COVID around the world.

[00:35:20]>> Mhm.

[00:35:21]less in the United States and more in other countries, which is a different topic, but uh well, there's more people in other countries, but the the thing is is that they can't prove it. But the people who got type 1 from COVID, one of the ways that we can tell a type 1 A from a type 1B, the autoimmune versus when your autoimmune system kills your beta cells, typically this takes some time. And during this these stages of progression, you lose more and more uh beta cell mass. And once it goes to a particular threshold, suddenly you get DKA, you go into the hospital, you get revived. What do they do? They run an A1C on you. With your A1C, typically most diabetics will say, "Yeah, my A1C was like 13."

[00:36:15]>> Mhm.

[00:36:15]>> People get type 1 diabetes from nonautoimmune.

[00:36:19]They get DKA, but their A1C is like six.

[00:36:24]>> Oh.

[00:36:24]>> Because they didn't have it long enough.

[00:36:27]their 90day average was perfectly fine.

[00:36:31]It just happened acutely at the very last minute. The autoimmune system doesn't work that fast, right? So, what we have are people who were brand new, newly diagnosed, don't know why it happened, but their A1C is low. They can't prove it.

[00:36:48]And just not to go on a COVID tangent, but CO also could could trigger the progression of stage two to stage three.

[00:36:55]Just the same way the stress of the flu or the stress of going to college or divorce or your car accident also helped progress you from stage two to stage three.

[00:37:05]>> Well, look, at the end of the day, you have these natural killer cells that are trying to kill the COVID. They're killing everything, right? So, this the stress from everywhere. And if you did have autoimmunity, it would just accelerate it, right? You can have both, right? Two things killing these beta cells at the same time, right? So the fact when when we say idiopathic, by the time you have type one, >> we can't retrospectively go back and look at what happened because it could have been anything. Now there, and when I say anything, it's like cancer drugs or a prim. I met a guy who got type one uh because he was on um you know the uh the drugs for his for his >> Yeah. Um >> I have a friend stomach cancer.

[00:37:52]>> Yeah. I have a friend whose mother went through that.

[00:37:55]>> Right. So there's all sorts of things that can kill beta cells that are not autoimmune.

[00:38:00]>> Yeah.

[00:38:00]>> 22% of type 1 diabetics are not autoimmune.

[00:38:05]>> Okay.

[00:38:06]>> Now it's not evenly distributed around the world. Um, most most white people have autoimmune and most non-white people who are type one have non autoimmune, which is an interesting thing. 15% of black Americans are not auto not autoimmune. And um yeah, so anyway, we can I did a whole article on the on on this and and >> which also means um tell me if I'm correct.

[00:38:38]>> That means that if you gave someone who's non-autoimmune a transplant of eyelet cells and then you gave them immunosuppressants, it wouldn't work because it's not the immune system killing the cells, it's something else.

[00:38:53]Well, let's we'll get into that once I start talking about autoimmunity and so forth because remember the the beta cell the uh cell source the eyelet source is different. So uh anyway let let's talk about that later but again the listener needs to keep in mind autoimmunity is not necessarily on >> and even if it is on it's not necessarily active.

[00:39:18]>> So think about um lot of patients people who get late onset. So there now that we are starting to understand this what we can look for in a test although it's not streamlined they're starting to develop these now they're starting to test for the actual te- cell activity. So when people look for um autoimmunity, they're looking for your uh antibodies, right? We're familiar with all the different antibodies.

[00:39:50]Antibodies is a byproduct of the beta cell having already been killed.

[00:39:56]>> They didn't do the killing. The beta cell was killed. But we can detect the autobodies that are still in our system.

[00:40:03]So if you detect autobodies, that means you had autoimmunity at one time. But it does not say that you still do.

[00:40:12]>> So one of the things that we have found by what you do is a simple blood draw.

[00:40:19]Put it in a petri dish. I'm really oversimplifying but this is basically the >> the science. You put it in a petri dish.

[00:40:26]Then you introduce >> um beta cells and you see what they do.

[00:40:32]>> If the tea cells start attacking them, you go, "Oh, that person's autoimmune."

[00:40:36]if they don't, >> they're not right.

[00:40:39]>> Okay, so this is a it's a lot more laborious than that and there's a lot of other things that can offtarget, you know, whatever. But but basically, these are the assays that are currently in development and there are currently in development alongside of companies that are developing immunosuppressent drugs.

[00:41:00]So people who want to develop something like what Eladon has done, they're doing these kinds of tests but not realizing that what they're developing is a really elegant assay that can be used throughout clinics. Just when you get your blood drawn, you can say, well, what's the threshold of my type one?

[00:41:20]What they have done with some of these early things is they've perfectly identified which um patients have really low autoimmunity. Lada.

[00:41:33]>> Yeah.

[00:41:33]>> So if your autoimmunity is low, you become a much better candidate for getting some eyelet transplants because you don't need very toxic autoimmune suppression. I want to I want to explain that in um a different way for listeners. So, cuz you you taught me about this over the weekend that there's kind of like this spectrum of autoimmunity. And by autoimmunity, we mean the immune system attacking your beta cells. And some of us have a really high autoimmunity, which means our immune system is like like really aggressive against those beta cells, killing them very quickly and aggressively. And then we have LATA patients type 1.5 and the attack on the beta cells is slower and less aggressive and which is why it can look like type two for 10 years.

[00:42:26]>> Yeah. And just think of it think of the fact that these lot of patients how long did they have type one before they were even diagnosed.

[00:42:37]>> Right.

[00:42:37]>> Right. They could they could go weeks and months without taking insulin. We can't, right? I'm not trying. I don't know. [laughter] I don't want to see.

[00:42:47]Hey, >> I'm not that hour.

[00:42:51]No. But yeah, I think people don't realize when they when they develop lad that they've been autoimmune for potentially decades, but it was just when it finally hit a point of lack of insulin production that their blood sugars started to rise that it was identifiable and often misidentified as type two. It's oh it's just horrible how misidentified it is.

[00:43:14]>> But anyway, that's uh so autoimmunity. That's important.

[00:43:20]>> It's a range of autoimmunity. And because we have a range now, you can foreshadow where this is going. We want to customize the the cure for those in different ranges.

[00:43:35]There's no sense in giving somebody with intense toxic autoimmune suppression drugs, not autoimmune suppression, just immune suppression drugs for somebody who does doesn't even have autoimmunity.

[00:43:49]>> Right? Right >> now, it does mean we have to give them eyelets that are their own eyelets, not cadaavver eyelets, not stem cell grown from some other line. We want to stem cell their own eyelids, right? So let's now talk about um that right. So people might be very interested to hear this but it's important to understand for context there's something called the total pancreattomy pancreatonomy I can't talk eyelid auto transplantation it's called tpi tp i a t >> okay >> 1977 the patients own eye so people with pancreatitis they have to remove their pancreas there's nothing they can do to save the pancreas. So what they do is they remove the pancreas, take out the eyelets completely, put them in the liver, and now they're cured. They don't have type 1 diabetes.

[00:44:54]>> Right.

[00:44:55]>> Right.

[00:44:55]>> They've removed the they the whole pancreas. They've removed it. Took out the eyelets, put it in the liver. What did this establish? It's established that you can take eyelets out of the pancreas and put it in the liver.

[00:45:10]>> Mhm.

[00:45:10]>> And they're not diabetics. This placement problem that we talked about seemed to be the cure, right?

[00:45:20]Um I go on a monthly type 1 diabetes hike in the Bay Area. If people are interested, we'll try to find out, you know, where I go on. And you know, there's usually 20 or 30 of us and we're all talking about this all the time.

[00:45:35]>> So, um, one of the women who was on this had a TPI.

[00:45:41]>> She had severe uh uh uh pancreas uh uh problems, >> had her beta cells removed, put back into her liver, but for reasons that are completely different, the her disease lasted too long. They couldn't recover enough beta cells, so she was just a type 1 diabetic.

[00:46:01]>> Yeah.

[00:46:02]>> She shocked everybody in the group by saying, "Oh my god, type 1 diabetes is the best thing that ever happened to me.

[00:46:08]It is so much easier than living with pancreatitis. The pain every day." And she would just go on and on. Wonderful woman, very positive in her disposition.

[00:46:19]But it was shocking for all of us to hear somebody who was thankful for having type 1 diabetes that it was so much easier to manage than what she had before.

[00:46:30]>> You know, it just it's just one of those things. And I've heard that from other, you know, cancer survivors. So, it's better than the cancer I had, you know.

[00:46:38]So, I don't know. It's just [clears throat] something to think about. Anyway, >> yeah.

[00:46:41]>> Yeah, that's right. So what this procedure taught us is that we can put eyelets in the in the um in the liver.

[00:46:50]So what that lead to the Edmonton protocol in the year 2000.

[00:46:55]>> So what they did is instead of taking somebody's own >> beta cells cuz they're diabetic they took kadavaric donors people who died they donated their organs. We took out their beta cells, their eyelets, and put them in the liver exactly like a TP uh patient would put them on immunosuppressants. The same kind of immunosuppressants. It's already done for whole organ transplants. Nothing new, but they did it. And it was the very first time that eyelets were transplanted into uh uh cadaavver eyelets into a type 1 diabetic and they were cured. Right. So the the results were just amazing and they were talking about it in the year 2000 exactly the way we're talking about eldon today.

[00:47:48]It's a cure. We now can do this. All we have to do is just cateic eyelets. Just put them on immunosuppressants and everything's fine. But of course that was just the first year, the first two years, the first three years. But then the problem started happening, right? So the A1C started going down. The autoimmunity started coming back. The all the toxicity from the immunosuppressants just wasn't working.

[00:48:17]So it was never intended as a cure. The scientists didn't want it talked about as a cure. It was it was just let's show that we can even transplant these things. M >> so despite the fact that it was considered a cure, there is a product right now today that people can do. It's called Lentidra, right? It's exactly the same procedure. If you want to be cured of diabetes today, you can just do that.

[00:48:48]It's FDA approved, but you have to be eligible, right? So that means you have to have such severe hypoglycemia that you're on the brink of death. usually other things. It's extremely hard to qualify to qualify for.

[00:49:04]>> So, I need to we need to dig into that for a second because I get so many I mean, I've gotten just like three in the last day uh messages from parents saying, "Is there a cure? Because I would do anything to cure my baby girl, right? Or my my 14-year-old son, we live in Australia. We will sell our house and we'll move to the US if you can connect me with the people that are running this cure." Can you tell those people why Lantidra is not the ideal cure for their child or is it like can you talk to those people?

[00:49:37]>> Well, first of all, they would never do that to children, >> right?

[00:49:40]>> Um, you really have to be very late stage. You you >> because the FDA knows that the cure can be worse than the disease.

[00:49:50]>> Yes. that your disease your disease risk has to be so imminent that what you're going to live with the biggest advocates for a cure are parents. They're not the diabetics. Now, of course, we all want a cure. We all are big advocates, but and and maybe I shouldn't say that that they're bigger advocates, but they're certainly the most active and the most vocal. They're the ones where, you know, my mom, you know, [laughter] when I was diagnosed, my mom immediately started giving to the JDRF, which is now like through T1D, and we started learning about all these things and they always told us in the 70s, a cure is only five years away, you know.

[00:50:32]>> Um, so the >> it your child is I have a child. I know that feeling.

[00:50:43]>> Yeah. Um, so to answer your question, just say, you know, look, at the end of the day, the things will be available for a cure before your child really suffers from long-term complications.

[00:50:57]But don't pretend that that's going to happen. You still have to be healthy.

[00:51:03]You don't want to be unhealthy. One of the things I say to people is you don't want to be so unhealthy that you want to be cured. is that cure to carry with it.

[00:51:16]>> Yeah, of course. I mean, we we need to take care of ourselves while we wait for the cure. But I think what those parents what those parents are facing in that moment when they're messaging me is >> that learning how to manage insulin is so overwhelming at first and it gets less overwhelming as time goes on. It doesn't become easy, but it becomes easier than those first few years. And so all they're thinking is my child's life is like ruined by this diagnosis and I need a cure when it's so hard to convince them that hey if you buckle down and you guys approach this like scientists you take your insulin you see what's working. You talk to your healthcare team about what's not working. You learn how to adjust your insulin. You study the little factors.

[00:52:03]You've got this massive type 1 community to learn from that life with type 1 can be very full, very wonderful and very long and that is still better than the amunosuppression therapy that comes with lanted >> correct and probably a lot of other things coming in. I think the the one bow that I would put on the top of it is that the reason why I believe that the reason why everybody, parents, us, everybody feels the way we do about management is because we're probably a little over obsessed with getting the numbers right.

[00:52:50]>> We think more damage is being done to our body if we're not perfect than the actual damage is. M >> and so I have a series that I'll be publishing soon on uh type 1 diabetes distress long, you know, history, you know, everybody knows about it. It's been well studied and well researched.

[00:53:11]But one of the takeaways from this is we're focusing so much on getting things right because we're so afraid of the consequences.

[00:53:21]>> Yeah.

[00:53:21]>> The fear is just not justified. So, um, the obsession can happen.

[00:53:28]>> Yeah. The obsession with the 90% in range. And I got a message from a parent who's had their child's CGM range set from like 100 to 140. And I'm like, "Oh my god, you got to you got to relax."

[00:53:40]Like, this is a long game, right? Like you got to relax and >> Right. Right.

[00:53:45]>> Yeah. Yeah.

[00:53:46]>> Okay. So anyway, that's that's a whole another topic. But in so far as the way a cure should be perceived is, you know, once we start going down this road of um understanding autoimmune, you know, the the degrees of autoimmunity that people have, the aggressiveness, >> you know, the irony is is that the hardest people to cure are the people with the most aggressive autoimmunity and those are the new diagnosis, right?

[00:54:16]it just as time goes on, if you're lucky enough to have your autoimmunity start to wayne as evidence shows that it seems to be the case, we're looking at cadaavvers. We're looking at people who, you know, die or go through clinical trials and we're finding autoimmunity for type 1 diabetes just wanes across the board. And we don't know it because we don't have any beta cells in us to they don't grow back, right? Right. It's not like other It's not like other autoimmune diseases where when it waines then you be healthy again.

[00:54:51]>> It's almost like I'm kind of picturing like uh you know your house burnt down and it burnt all the grass around it and eventually the grass grows back but the house doesn't come back. It's like this.

[00:55:03][laughter] >> But wait, I have a question. I have a question.

[00:55:07]>> Yeah.

[00:55:08]>> Can you explain to people what's similar about Lantra versus Elodon's therapy and what's different?

[00:55:15]The only thing that's different is the immunosuppression and what makes eldon and that's in my very next section.

[00:55:22]Let's go right into immunosuppression and and uh and let's get into that. So um let's see. So uh what do we have here? Uh eldon right?

[00:55:36]So 100% insulin dependent uh in the in 10 patients uh A1C 5.3 >> and sorry insulin in 12 patients 100% insulin independent.

[00:55:50]>> Yeah, >> right. Um but 10 of them had an A1C of around 5.3 is what I have. Anyway, it's I'm just talking about statistics. Yeah.

[00:56:02]>> Um what they're basically doing is they took exactly the same cataic beta uh eyelets putting them in the liver. So again standard protocol the only thing they changed is the immunosuppression and what teladon is so great as >> um tac tacimus tacimus I heard it >> yeah pronounced in so many different ways I >> Ally who takes it Ally Duggar who takes tacimus for her pancreas transplant she says tacrolmus so that's why I say tacimus >> right okay so factor limits. That is a $7 billion uh market right there. It is used for whole organ transplants. It's used for all sorts of things, but it's extremely toxic. So, what does it do? It does bad things to your kidneys and so on and so forth. But one of the um uh the the the what what al one of the things that it does that is so deadly is that it cross links uh platelets and can cause clotting and tacrolinus in many patients they get these clots they can die from them they it can just do all sorts of other things. The only thing eleon does is stop that platelet cross-linking. That's the only thing it does. But it's an amazing feature, right? The fact that it does it, tego does that. And so I have a whole separate article on aladon that explains this in greater detail. The fact that it takes that away means that the toxicity is much much lower. Right? Okay. So >> it we don't know how low yet. Right. We don't know. Sorry, we don't know how low in type one. We do because their primary market is whole organ transplants.

[00:58:02]They're happy to look. We make a drug.

[00:58:04]We'll give it to anybody who thinks they can use it. Type one. Sure. You know, it's not like they care. I mean I I mean they do care. I'm I'm not saying otherwise. I'm just saying it's not like they prioritize one particular therapy over another in so far as their business. their business is we have a very a far less toxic drug. So this is why that company is been seen as so valuable because they're about this tiny little 35 person company is going to disrupt an 8 billion industry, right?

[00:58:41]People will be healthier and >> okay so let me let me um kind of regurgitate this. By the way, it's already approved for it's already approved for uh kidney transplants and liver transplants. These trials have been done.

[00:58:56]>> Okay.

[00:58:57]>> It's already approved for use in kidney transplants and liver transplants as an ongoing >> that's from my notes and and I don't you know if it's not approved it's so close to it. I know the Bestow trial is the key one that has shown to be everything.

[00:59:16]So, as a company, they're just riding the wave on this and and they should.

[00:59:21]It's an amazing drug because of the toxicity.

[00:59:24]>> Can I ask you a few questions on that?

[00:59:26]So, are they basically hoping to take tear and replace tacimus in full organ transplant?

[00:59:36]>> Yes.

[00:59:36]>> Is that the goal? Okay. So now I have another >> and in eyelid transplants.

[00:59:41]>> Yes.

[00:59:42]>> And in transplants, right?

[00:59:43]>> Okay. So why >> wait I have a question.

[00:59:47]>> Why in the protocol for the 12 participants in this T1D elements in the beginning?

[01:00:01]>> I don't know.

[01:00:03]>> Okay.

[01:00:03]>> Now it could be that they were trying to do AB testing. Remember this is the first trial. This is like >> the first of many. They have to run this a lot. They have to take out certain things. They have to you know the it it could be the establish uh the established protocol was this. So we need to show what it was alongside of what we did.

[01:00:27]>> Uh and and they took it alongside uh two or three other immunosuppressants at the same time as well. I don't exactly know or remember, you know, uh you read these things enough and sometimes it's not >> I mean I know I've heard other companies explain that the protocol that they had to prepare the 12 participants in Eladon's trial, the protocol they followed to prepare for their transplant is kind of the classic transplant protocol. So that is a good theory >> because you want you want to compare, >> right? You want to compare what is known to e not necessarily work but the known baseline. We know cataic eyelets, we know liver and we know tacrol limus.

[01:01:11]>> Yeah.

[01:01:11]>> And we know it worked for the induction.

[01:01:13]So now let's see how tegoart works for the ongoing protection.

[01:01:18]>> Exactly. That's that's exactly right.

[01:01:20]And just not enough time has passed.

[01:01:22]Right.

[01:01:22]>> But everybody says hey this is a new cure.

[01:01:25]>> It's not. it really I mean it's the same cataric eyelet and it's the same liver transplant. So if there's something called the collaborative eyelet transplant registry and their 12th report 1400,477 recipients more than 8,500 person year follow-up insulin independence at one year and um many of them matching all of them are matching Elodon. So, Elodon is just doing yet another trial following exactly the same 25- year baseline. So, these 10 patients are just added to the 1477 patients that have also already been cured. Nothing new to see here in so far as a cure is concerned.

[01:02:21]>> Okay. I have to ask a bunch of questions on that for listeners. So, you're saying >> let me just finish the one. Hold on. Let me the in so far as a cure is concerned their A1C insulin independence all of them is identical to the other 1500 people who've already had it done. The only difference is the immunosuppression part is less toxic. We don't know how long that'll last. We don't know how long it'll it'll affect the autoimmunity part because it's only TE-C cell activity.

[01:02:52]>> Right?

[01:02:52]>> We're going to dig into that >> T- cell in general, right? So that's a whole different thing. There's a lot we don't know. What we do know is that some of the toxicity is a lot less.

[01:03:03]>> Okay. So, do we also know that the 12 participants in Elodon's trial are taking myic another form of amunosuppression therapy? Is that used with Lantidra?

[01:03:17]>> Don't know.

[01:03:19]>> Okay. Was it used in the other 1500 patients that you just referenced?

[01:03:23]>> Don't know. No. Remember these are these are collaborative eyelet transplant registry.

[01:03:30]>> So every trial that was talking about they're triing something different.

[01:03:36]>> So all of these trials are trying something different.

[01:03:40]>> Okay. Okay.

[01:03:41]>> Right. So different immunosuppression.

[01:03:44]It could be >> Yeah. Okay. So everybody's just being [clears throat] compared to everyone that's received an eyelet cell transplant over the years.

[01:03:51]>> Right. If you've received a NYU transplant, you're in this registry.

[01:03:54]Now, what did they use? We don't know.

[01:03:57]>> But we do know that all of them got perfect A1C. They had, you know, uh the the beta cells were working. The eyelet cells survive. The eyelets survived.

[01:04:10]>> How long does it tell you how long?

[01:04:13]>> Yeah. Okay. It probably does, but I was just looking at just the the headline, you know, just at a year, at two years, at five years. Yeah.

[01:04:23]>> Everybody's is is roughly the same. In other words, >> so this gets back to that very first thing I talked about. The immune system is really persistent. If it has it in its mind that it's going to kill these beta cells, it's going to find a way to get there >> and it's going to work around it. It's going to, you know, mutate. We we there's evidence that TE-C cells themselves will mutate as necessary in order to to reach their targets. And of course the the the the problem with with that mutation is off target attacks.

[01:04:58]They could attack thing. This is why there's other autoimmune diseases that are popping up in some cases. So once you're trying to suppress the immune system, you're really messing with a very formidable en enemy there, the less toxicity. Great. But you still have the same immune problem, right?

[01:05:19]>> Okay. What do you make of the And you might be addressing this soon. What do you make of the line, it will soon be known, there's two two ways I've been told this. It will soon be known that Tegopoubart can work as a monotherapy or also the line you know we plan to make this a subcutaneous injection you can take at home >> because people are let me add let me add >> I hear this >> and what a lot of people are expecting based on the hype and the influencer media about Elodon's trial with 12 participants is that this is just kind of a bunch of fluff with these other amunosuppressants and very soon they will demonstrate and approve this drug taken at home within an injection all on its own and that will protect any transplanted cells.

[01:06:19]>> That might be possible. They're certainly developing that and given that the drug is already being used for uh liver and kidney transplants.

[01:06:30]If they do come out with that, those are the people who are going to use it.

[01:06:34]It'll be approved.

[01:06:36]>> Okay, that's the end of part one in our 2hour interview with Dan. In part two, you can find that next. We're going to be talking a little more about the research that's going on around the world and the FDA approval process, phase one, phase 2, phase three of a clinical trial and what that realistically looks like even if it's getting, you know, fasttracked and the FDA is like go do this as quickly as possible. All right, so tune in for episode two for part two, excuse me.

[01:07:10]Thank you for listening to another episode of the Diabetes Nerd Podcast. If you're looking for more support, you can find Diabetes Nerd on YouTube. You can find my books on Amazon. I have books on pregnancy, on exercise, on burnout. My newest book is called Every Day with Diabetes. It takes you through 365 tips to learn a little bit about diabetes and insulin every single day.

[01:07:40]You can also check out the Diabetes Nerd Network. This is a completely free to join community where we're trying to keep you in the loop on upcoming clinical trial opportunities and other diabetes research. You can find all of this and more at diabeteserd.com.

[01:08:01]Thanks for listening. [music] [music] >> [music] [music]