#48 Stimuli Responsive Glucagon and T1D Research with Dr. Matthew Webber

Episode 48 of The Sugar Mama's Podcast features Dr. Matthew Webber, an associate professor of chemical and biomolecular engineering at the University of Notre Dame. He is currently in charge of a team that is studying, among other things, stimuli responsive glucagon.

This emergency glucagon or "smart glucagon" as I like to call it is a gel based technology that is injected into the body. It is able to sense when blood sugar levels are dropping to a dangerously low range and release glucagon in response to that. In other words, it has the ability to raise blood sugar levels automatically to treat lows in insulin dependent  patients such as those living with type 1 diabetes.

Research like this is amazing to me and I can't wait for you to hear all about. When your done, if you want to know more about what Dr. Webber and his team are doing in their research lab, you can check them out on the Webber Lab website.

If you want to see the commercial mentioned in the episode that aired during a Notre Dame football game (this is how I found Dr. Webber) click HERE.

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Below you will find a transcript of Episode #48.  The show's transcriptions are created by an automated, electronic service that is based off of an uploaded audio recording. Although the transcription is largely accurate, in some instances it is not correct or is incomplete due to inaudible portions of the recording or due to computer-based transcription errors. The transcriptions should never be treated as an authoritative document or record. Again, nothing that you hear or read on this website, in the show notes or in a blog post should be considered medical advice or advice in any way, shape or form. Always consult your physician before making any changes to the way you manage your or someone else’s health. To see our Privacy Policy, Disclaimers and Disclosures in full, click HERE. 

Transcript

Katie: 0:00

Hey there, sugar, mamas, sugar, daddies, grandmas, grandpas, aunts, uncles, friends of T1, D anyone. Who's a caregiver for a child living with type one diabetes. Welcome. This is episode 48 of the sugar mamas podcast. And today I'm talking with Dr. Matthew Webber from the university of Notre Dame. He's going to tell us all about what he and his team are doing in the field of type one diabetes research. It's pretty awesome stuff. Let's get started. You're listening to the sugar mamas podcast, a show designed for moms and caregivers of type one diabetics here. You'll find a community of like-minded people who are striving daily to keep their kids safe, happy, and healthy in the ever-changing world of type one. I'm your host and fellow T one D mom, Katie Roseboro. Before we get started. I need you to know that nothing you hear on the sugar mamas podcast should be considered medical advice. Please be safe, be smart, and always consult your physician before making changes to the way you manage type one diabetes. Thanks. Hey everybody. I am here with Dr. Matthew Webber today, and we're just going to jump right in. I'm really excited talk with you today, but I'm going to let you introduce yourself and tell the listeners what your connection to type one diabetes is.

Dr. Webber: 1:26

Yeah. So I'm happy to be here today and talk to you a little bit about our research. So. Faculty member at the university of Notre Dame. I'm an associate professor of chemical and biomolecular engineering. I run a research group at that present consists of about 10 students that are pursuing their PhD under my direction, as well as seven scientists who already have PhDs and are working with me for additional.

Katie: 1:49

Okay.

Dr. Webber: 1:49

research group is, is really focused on the idea of making new materials and devices that can make the management of blood glucose and diabetes a little bit more autonomous. And so thinking about strategies to deliver things like insulin and glucagon in a way that is sensitive and responsive to need, which need being the level of blood glucose. Right. And so we're thinking about. Strategies for better. Long-term controllable glucose using insulin strategies for preventing serious hypoglycemic episodes with, with onboard glucagon that could be deployed if needed in the event of a serious hypo event. And thinking about other ways for doing better glucose detection and glucose monitoring using using materials and device.

Katie: 2:32

long have you been at Notre Dame?

Dr. Webber: 2:34

But in Notre Dame almost a little over five years. And so I started my research group here the fall of 2016

Katie: 2:40

And have you been working in the type one diabetes sealed with, in terms of your research since you started there?

Dr. Webber: 2:46

at Notre Dame. Yeah. We've been doing, we have we have other angles of our research as well. We, we pursue a few other types of things here. But a large portion of our research group, especially reflected in the, the funding and the awards we have are in the diabetes space. And so we're very interested just generally in stimuli, responsive materials, materials that can do interesting things when exposed to a stimulus. And in the context of diabetes, that stimulus is glucose. For other things, maybe we're thinking about, you know, other, other interesting disease markers, or other things for other therapies or we're designing, our primary focus is in glucose response.

Katie: 3:18

In case listeners are wondering, I found Dr. Webber through a commercial that I saw that was aired during a Notre Dame football game. And in the commercial, it kind of started by interviewing parents of a probably six or seven year old boy that has type one diabetes and then kind of transitioned into talking about how Dr. Weber and his team at Notre Dame are researching a, the commercial. Referred to it as a gel based technology that can detect dropping levels of glucose in the blood and then release the necessary amount of glucagon to, to stop that to safely stop that. So, it sounds like you're doing a lot more than just looking into this gel based product, but tell us a little bit about, about that.

Dr. Webber: 4:06

Yeah. Glucagon project is one that we're kind of trying to take a new spin on, on the delivery of therapeutics and the glucose responsive way. And so I would say historically in the field of diet, The glucose responsive insulin has been kind of a promise for, for the last several decades that is still in development and maybe isn't isn't fully available yet, but the idea there would be you'd have an insulin that could be mobilized or have its potency increased as glucose levels go. And so what we've been thinking about instead is reverse engineering. A lot of those sensing and response mechanisms that have been explored for glucose responsive insulin, and instead designing materials where they are in fact stabilized in the presence of glucose and then destabilize or fall apart or degrade in the absence of glucose or under, under low glucose conditions. And so that's been kind of the, the motivation for our work was take what we know. About glucose, responsive insulin things that I've worked on, you know, for years as a postdoc and my own training and then try to flip that and do glucose responsive glucagon. And so the gel you're speaking of is kind of our first pass at this, this technology. We have a system that we can inject. Under the skin, we've done studies through mouse studies at this point. And so there's still a lot of development left to be, to be done on this particular technology, but it's an easily injectable gel, very low viscosity goes in, goes into under the skin, and then it holds glucagon in place and sort of a Depot there. But if in the event of a, of a hypoglycemic onset, which we stimulate by an insulin. The gel just to solves and the glucagon that was encapsulated comes out. And so in our models, when we, when we do a hypoglycemic induced event by insulin overdose in these mice, we find that the blood glucose levels don't go nearly as low when they have our device on board. They recover a lot faster, importantly, they don't die where in the control cases, they sometimes die. And so. We're hopeful for this technology. I think there's still some things that we need to to try to improve, but we've now got kind of generation one of this technology demonstrated, which is sort of a new concept in this, this glucose responsive therapeutic space hoping to build on and make things that would be a little bit more viable. So there's issues with the current technology that we know about. We're trying to engineer those issues out with a series of iterative improvements and trying to make a better technology in the end.

Katie: 6:29

So how does that work physiologically? what, what about this gel based technology triggers it to dissolve and release the glucagon. I mean, you said the rising or the dropping, excuse me, the dropping blood sugar levels, but I'm just curious to know, like at the cellular level, what, what triggers that.

Dr. Webber: 6:47

Yeah. So we're using glucose sensing chemistry. And we're using also enzymatically responsive enzymatically, I guess actuatable chemistries, I could say. And so when you think about like how a continuous glucose monitor works or a handheld glucose meter works many of these function on the basis of an enzyme that's known as glucose, oxidase and glucose oxidase can convert glucose into. Gluconic acid and hydrogen peroxide. so your continuous glucose monitor and your handheld meter are actually reading the hydrogen peroxide product of that glucose oxidase conversion. And so this is known technology for, for being able to measure blood glucose normally. And so what we do in our first iteration of this is we've included glucose oxidase into our materia. To do the glucose sensing piece, but instead of actually detecting the hydrogen peroxide as your CGM or as your handheld glucose meter would do we're actually using the gluconic acid product to drive changes in our material.

Katie: 7:47

Wow. Okay. Very interesting. So is the idea that, you know, type one diabetics would inject this, like once a day, once a week, is it kind of like a long lasting insulin type of thing where it lasts for 24 to 48 hours? Or what would be the kind of the clinical of it?

Dr. Webber: 8:06

Yeah, I think that's still to be determined. I would say probably the most likely form factor would be, you know, a nightly injectable, for instance you know, something before bed time, you have a, you know, you have a shot of this stuff. You've got your glucagon on board at the ready in the event of some nocturnal hypoglycemic episode, which is the one. You know, cause parents and diabetics, you know, the most stress and anxiety and, you know, are the most lethal. Right? And then you've got this sort of at the ready in the event of some, a subsequent event. And so if it was that way, it'd be kind of a nightly thing. If the gel doesn't deploy for a hypoglycemic episode, you know, there'd probably be some low level of glucagon activity kind of released from the material over time, maybe over a period of 12 to 24 hours. And the material itself has pretty readily cleared. And so ideally that would be sort of just a, you know, you, it would, it would sort of clear, clear normally in the event that it wasn't actively deployed in their response to a hypoglycemic event potentially a little bit of glucagon activity associated with some leakage.

Katie: 9:08

Okay. earlier you referenced the glucose responsive insulin, is that what I've heard? People call smart kind of smart insulin, like where it only. we'll respond when blood sugar levels get too high. Correct. Is that smart insulin?

Dr. Webber: 9:21

I think that's probably similar. Yeah.

Katie: 9:23

Okay. Okay. And So this is, this is more of like a smart, a smart glucagon. So in, is it so smart that it would actually only release the amount to bring the glucose levels back up to like a certain level? Or what have you seen in the mice in terms of bringing them back up? You know, I'm, I'm assuming that you wouldn't want it to like skyrocket the blood sugars, but what have you seen.

Dr. Webber: 9:45

So our initial technology is admittedly not very smart. And so I think I think we have you know, issues. I think I mentioned, you know, we've, we've got some known issues. One of them is that the glucagon does leak out a little bit on injection. And so we do see a little bit of a spike initially on. Which isn't ideal, right? You wouldn't want to do anything to sort of confound or disrupt the insulin centered control blood glucose. we'd like to get that leakage down. And then I think we're thinking, you know, like but what we, what we see from there is when we do these insulin challenges, the depth, like the well that we would get in sort of the low point of blood glucose following the insulin overdose isn't. And then a couple hours after insulin challenged, they're back to a normal level. Whereas our control mice are still maybe cruising along at a 60 or a 70 milligram per deciliter level. So it's still pretty low. You know, we we're, we're in the, you know, one 20 to one 30 range, for instance, in our, in our prophylactic treated mice are mice that were treated before the challenge with our.

Katie: 10:45

So at what point in, in a

Dr. Webber: 10:47

Yeah,

Katie: 10:48

reading, would the gel respond and release glucagon? Like, is there a certain number, you know, could you translate it into like a number for where it would kick in.

Dr. Webber: 10:58

no, I think the challenge with the technology we're using is you, you can't really think about it like a light switch, sort of like an on-off kind of release. I would maybe think about it more in the context of a dimmer switch, where it releases more, the lower the blood glucose goes. And so it'll release summit 200 milligrams per deciliter, or at least more at a hundred. It will release more at 50 it'll release more at 25 it'll release more at zero. And so there's sort of, it's sort of, it's kind of increasing the release rate as blood glucose goes down. And so it's not like it would just kind of click on. I think that would be really nice. It may not be possible in the context of sort of the kinds of materials we're designing that have sort of that very sudden rapid event.

Katie: 11:38

Yeah.

Dr. Webber: 11:38

about other ways of having a more sudden and rapid event which we haven't we haven't disclosed really in that kind of stuff yet, but I think for now, what we're working with, you could think of as like a dimmer switch, right? No more or less released depending on what glucose level. It'd be great to get

Katie: 11:53

Okay.

Dr. Webber: 11:54

no release until, you know, you're at 55 milligrams per deciliter or something looking pretty dangerously low. And then thing flips on and gets you back up to one 20. I think that'd be really great. I think the engineering of that is considerably more complex from a injectable. Um, maybe, you know, certainly by hormonal pump or something like that might be able to achieve that kind of bolus administration upon hitting that level. are not, we're not able to do that with our, our formulation approach.

Katie: 12:21

Well, I mean, earlier you mentioned the whole not dying thing, which is it's a major bonus, right? I mean, let's be honest. That's kind of a. Biggest fear with having a type one diabetic child is that their blood sugar is going to get so low. That something really, really horrible and serious is going to happen. So, you know, ultimately to me, at least if they were having like a really severe hypoglycemic event in the middle of the night, I wouldn't care what number, any technology brought their number back up to. As long as it's within a, you know, a range, that's not going to send them into. Into a coma. But, and, and like you said, there's, you know, if it, if, if blood sugars do get too high, whether that's from, you know, nasal spray, glucagon, or injectable glucagon, or this gel based technology, then we have, have things to treat that too. Right. We can, we can bring it back down with insulin. So in my mind, at the moment, ultimately, it just, it doesn't matter. I just think it's amazing that you guys are working on developing this technology to have a smart glucagon It just would give us a lot of peace of mind to know that there's a backup system, right? I mean, our liver itself is a backup system, but in the, in these circumstances where you've overdosed on insulin, it can only do so much. Right. So it would be nice to know there's a, a backup to the backup system.

Dr. Webber: 13:33

Yeah, and I think that's that's key. And I also think, you know, Increasingly it's appreciated that. I think maybe an ignored aspect of, of type one diabetes and understanding the diseases that you know, we all know the beta cell, you know, is, is, is gone. And the, in the case of type one diabetes doesn't produce the insulin or the amylin. But the alpha cells also for whatever reason are pretty, are a little bit dysregulated, the ones that secrete glucagon. And so even sometimes those, those stores in the liver kind of that emergency backup. Aren't aren't properly utilized even even in type one diabetes because glucagon signaling for whatever reason is also a little bit dysregulated or kind of the responsiveness is, is dysregulated. And so I think that's actually very, and I'm not a biologist, but I think there's some interesting biology. That's, that's kind of starting to uncover some of the mechanisms of this alpha cell dysregulation and type one diabetes that is probably a whole other, you know, a way to understand how to treat. to control blood glucose. And so I'm kind of curious to see where that research leads as well.

Katie: 14:33

Yeah, so this is in the development phase with the gel based technology, the smart glucagon, or

Dr. Webber: 14:38

very early development.

Katie: 14:40

early. Okay.

Dr. Webber: 14:41

And so whenever I, whenever I do these podcasts, I'm always, you know, I'm always hesitant to oversell. You know, I've done a few of these now and I would just, you know, I say, you know, we're working on better technologies or we're trying, I think there's a, there's a hopeful future for better methods of blood glucose control in the future. We're not there yet. And so we're really, you know, we're, we're trying to get stuff that we would feel good about. You know, bringing to that next level, bringing into clinical use actually treating. And and, and we're not, we're not quite there yet. And so I always, I always feel bad when I do these things. I don't want to give people false hope or, you know, sometimes people don't always appreciate the, the runway to development of a new product or a new technology and getting that into. Into human use and kind of the stage of where we are. And so kind of by way of full disclosure, you know, we're, we're working, we're trying to make progress, but we're not we're not actively enrolling in clinical trials yet. For instance, we are, we're still trying to get the system to work and work better. And so I do I do like to sort of frame this in that context.

Katie: 15:38

Absolutely. No, I, these things obviously take a whole lot of time to develop and test and, and make sure they're safe and, and things like that. But what, so what would be next steps for, for this particular product?

Dr. Webber: 15:51

You know, I think like, I think as I mentioned, our first demonstration, I don't think is clinically viable for a few reasons. And so we're going back and we're, re-engineering a lot of that. And so from an academic perspective, we wanted to demonstrate this concept for the field that hadn't been demonstrated before. Now that we've done that, we're kind of thinking about, you know, okay, now can we make this better? How can we prevent some of this early leakage? How can we make the response faster? All right. Do you know, how can we make the response, you know, more appropriately tuned for, for the desired end point like glucose that may be. Following a hypo event. And so I think these are all considerations that we're going to, we're continuing to, to to take into the design of the system and tweaking different, different parameters and trying to make things better. We're starting to play with different ways of doing the detection of, of glucose which I think would be, would be key to driving, pulling costs of any sort of technology down. And then also just simplifying the end product and things like that. Or or we're always kind of working to re-engineer and, and and improve the system where we've kind of initially demonstrated.

Katie: 16:54

Yeah. Well, you've mentioned a few other areas that you're working on also in the realm of type one diabetes. Would you mind telling us a little bit about those also?

17:04

We're taking a super quick break from my interview with Dr. Matthew Weber. So I can tell you guys about the product of the week. I don't know about where you live, but where I live right now, it's next to impossible to find juice boxes, especially the tiny ones that we like to use. You know, the little apple and Eve brand ones with Sesame street characters on them. I love those because they're only four ounces of liquor. But they have around 13 to 15 grams of carbs. So I feel like it's good if you need the carbs to treat a low, but you're also really full, like maybe my daughter to say to meal and she can't physically fit more stuff in her body. That's why I like to use the tiny four ounce ones. Well, I can't find them anywhere. So I remembered the other day that we have these reusable plastic four ounce bottles that I got off of Amazon, like a year ago when my daughter was taking Gatorade. I didn't want to send her with a whole Gatorade because I didn't want her to drink the whole Gatorade. You know, when she wasn't supposed to, I remembered I had them. I dug them out. I've been filling them up with four ounces of apple juice, same brand, apple, and Eve apple juice, but the kind that comes in the jug instead of the little juice boxes and it works great. Plus it's probably better for the environment, right. Creates less trash and it's cheaper. I will put the Amazon affiliate link in the show notes so you can check them out for yourself and maybe consider using them. If you haven't been over to the sugar mamas podcast, buy me a coffee, Paige, go check it out. Buy me a coffee is a way for listeners like you to support the show hosting and producing a podcast is so much fun, but I'm not going to lie. It takes a lot of work to make this thing. Each and every week, your gift through buy me a coffee can be a one-time donation, or you can sign up for one of our fun membership levels starting at only$1 a month. Every single cent donated through, buy me a coffee. We'll go to making this show, come to life each and every week as always. Thank you so much for your support. It means the world to me, let's get back to the show.

Dr. Webber: 19:02

Yeah. So we have, I guess, kind of a broad glucose responsive material interest in my group, I think, as I mentioned in, so we're thinking about. No, I think you called it smart insulin, you know, injectable insulins that have glucose tuneable potency or glucose tuneable availability. Right. So you could imagine. That's something where my insulin is in a Depot and is sort of sequestered there until it's needed. And then it is released from that Depot. And can we do something like that where you could meet sort of the, the long, long lasting needs that you would get from your long acting insulin, as well as your prandial needs that you get from starting your fast insulin? Could we do that all with one source? System right where you'd have a single injectable that met both your basal and your prandial needs kind of in a single shot. And so that's one of our goals. And then kind of building on that. Can we do something a little bit more biomimetic with insulin formulation? And so I think one of the key things that is that is probably not considered enough in a. Efforts to control blood glucose is the role of amylin and blood glucose control. And so, you know, I mentioned the beta cell when it is destroyed by the immune system to, to, to lead, to type one diabetes onset the beta cell produces insulin and amylin, and both are secure. In response to a high glucose state that they work together to, to lower blood glucose. But amylin does some interesting things with suppressing appetite and with reducing postprandial hypoglycemia and with modulating glucose absorption in the, in the gastrointestinal system. And yet when we treat diabetics for the most part, we don't, we don't replace that animal in signal. We do it with insulin only injecting. Or pumps or whatever it might be. And so one of the areas of interest for our group, as well as co formulating insulin and amylin AML, and the, the, the pharmaceutical version of amylin is known as pramlintide. And so a lot of, I, you know, the stats, I don't know the exact numbers, but the stuff I've seen in different places or in some of the meetings I've been to what suggests that only a few percent. Of type one diabetics that could be doing, taking co formulations of insulin and pramlintide or actively doing that, our co delivery, I should say. And part of the issue is you can't get them in the same injector, cause they're kind of, they're incompatible under the same solution conditions. And part of the issue is cost. And part of the issue is just sort of maybe, you know, not not pervasive enough use and these kinds of things. But I think that there's probably something to be gained. Better glucose control by providing a more biomimetic therapeutic replacement than just the insulin only. We need the insulin for sure. The insulin is the key piece without insulin. We can't control like. But the amylin does something. It helps. It helps control blood glucose as well. And we, we, I think at present, ignore that. And so we're thinking about ways of getting those in the same vial of getting those in the same Depot so that they can do their work together the way they do in a sort of a normal, healthy functioning pancreas.

Katie: 22:05

Yeah, I am amylin slows down digestion. Doesn't it slows down the absorption of glucose. Is that right?

Dr. Webber: 22:11

Yeah, it it does some interesting things with the gastrointestinal system. Like I said, it also is known to prevent some of these post-prandial hypoglycemic events that you can see you know, when, when dosed. And so I think there's some added benefit. I mean, it's you know, you need the insulin instance key, you know, and, know, get it, you, can you get some, know, some Delta, some increase in, in performance from adding this. You know, how do you get people to, to use that? And potentially it's not a, a viable approach for a lot of people who are doing like a pen injector of insulin to then have to, you know, do their insulin and do their You know, now they've gone from, you know, four or five shots a day to eight, 10 shots a day, whatever it is, right. If you have to do two shots every time maybe that's. You know, and only one of those is key to keeping you alive. The other one just improves function. And so I think that there's potentially some challenges there to implementation, which we're trying to, to knock down some of those barriers.

Katie: 23:07

Yeah, I looked into pramlintide. I didn't realize that was the prescription name of it, but for, for my daughter, who's only nine. She has type one. She's the one with type one diabetes. And in, I think it's only 16 and over, or maybe 18 and over, it's only approved for older. Kids or young adults. So that was not an option for us at the time. And I I've heard, I don't know but I've heard that some of the side effects can be rough.

Dr. Webber: 23:29

Yeah, I know not nausea can be kind of bad with it in some cases. The dosing of it is a little tricky and it's probably a little bit more person dependent. I think like the exact ratio that is released from the beta cell and I in a healthy state between insulin and amylin. Amylin is a little bit. Varies a little bit from person to person. And so I'm trying to match that therapeutically as can also adds a whole other challenge. I think that, you know, I think people are still working to address so that there's some companies out there that are working on these stable amylin, variants, stable variants that potentially could start to be put into a co-formulation with insulin, et cetera. So.

Katie: 24:06

Yeah, I think that's something for parents which are, you know, the majority of my listeners, caregivers of type one diabetics to remember. You know, the beta cells that get destroyed in the onset of type one diabetes, they do, they do so much more than just produce insulin. Which is why being a pancreas is so incredibly difficult because there's so many factors that, that to consider and that go on inside the body. You know, it's not just the insulin production that gets destroyed. It's other things too, that affect how your blood sugars up and go down. And all those things are, are either of those, the the glucose responsive insulin. And then the, the con of combination of the insulin amylin are either of those being studied in, in animals yet.

Dr. Webber: 24:52

Yeah, so both of those, we have, you know, we were running animal studies yesterday. Actually we have some going on today, even with some of our glucose responsive insulin strategies. We've demonstrated ways of doing better glucose sensing with these materials and more accurate glucose response. We've got now some strategies where we think we can get, you know, 24 hour control that meet both the basal and prandial needs. Or we can, you know, we can simulate three meals and mice and the, you know, the blood glucose is corrected with each meal with, from a single dose that was, you know, hours prior. And so we have some early saves on that and then the insulin pramlintide this is something we published on. I know if my good friend Eric apple out at Stanford, we worked on this together and we published this. 2020. We took studies of that all the way through diabetic pigs. And so we have large animal data. They're demonstrating co-formulation of insulin and pramlintide in a single vial and, and, and improved control in diabetic pigs compared to insulin only compared to separate injections of insulin and pramlintide, which was a little bit surprising to us, but it actually giving them in one shot actually worked better than giving two shots right next to. And so there's a, there's some interesting, I guess, pharmacokinetic reasons for that we think, but yeah, this has been, you know, some stuff we've been working on for a few years now, so.

Katie: 26:04

Hmm. so. I'm just curious, like the, the one you're just speaking of where you were testing it and where You got it to the point where it was being tested in pigs. Like at what point do people say, okay, now let's try to test this in, in humans. I'm sure it takes years and years, but at what point do you say let's give this a go and in a clinical trial.

Dr. Webber: 26:21

You know, there's, there's a lot of steps, I think rightly so between where we are and where we would need to go there. You know, we would need to make materials in a, in a way that would be, you know, clean and sterile and fully validated and all of the synthesis and the characterization and all of those things. And that's, you know, that's typically an outside research kind of contract organization that would take care of that. That's not the kind of thing we would do in an academic lab. I don't have know clean rooms and students in bunny suits and kind of the sterile environments and those kinds of things to make the stuff that way. And so, you know, if we've got a technology that we wanted to get to work, we would need to go out and typically raise some capital to do the first stages of scale up and manufacturing under the sort of sterile and fully regulated and validated conditions. From there. Then we would take that filling that's, you know, kind of fully validated material, fully doubt, validated formulation, whatever it might be. we would take that and we would do a redo safety and toxicology studies in and typically large animals.

Katie: 27:24

Yeah.

Dr. Webber: 27:25

And maybe, maybe just validate, you know, quickly, the, the efficacy we saw in early in early studies was, maintained using this newly sourced batch of material. And then once you've got that batch that you verified safety and toxicology, and you know, it's been made in a very clean way. And these kinds of things, you could start to do a very small. Clinical trial, I think it would be the typical goal and each step of the way is getting more and more capital intensive. And so typically it helps to to launch either, you know, startup companies or partner with, with large. Large pharma companies or other sorts of people who work with venture capitalists, et cetera, to, to to raise the capital necessary, to get over each of those hurdles. And then you know, and so that's that period that I just mentioned to go from sort of my vibe at Notre Dame to, to early stage studies in the first few people could be on the order of a few years. If everything goes well and it could get derailed at any point along the process, right? We find out that the toxicology isn't acceptable or, you know, we're due. We find out we have some, you know, undesired, you know, toxicity arising in the liver and the kidneys or the blood work comes back and, you know, blood cells look off or things like that. And then this starts to kind of derail things pretty quickly. But assuming you get over each of those hurdles now, you know, maybe you're a few years to get to. With all of these technologies. And then that's like your first step in people, right. You're doing a very small stage thing. And then maybe you would do a larger trial and you'd study for efficacy and you'd have, you know, understanding of dosing and timing of dosing and best practices there. And then, and then you'd get to, you know, demonstrating how well it works against the standard of care. Right. Sort of the, what is the current gold standard and how well do we work compared to that? And so, you know, each of these processes, as yours says, you get down. The path further and further towards clinical use the costs go up quite a bit with each step. And so so it's, it's time intensive and capital intensive for sure.

Katie: 29:25

I think it's good for people to hear that though. Cause they, you know, we just don't realize these things just take so much time and so much money and I know you guys are working hard to. To get things, tested and, you know guess verified as quickly as possible, but I think it's good for people to remember. You know, we live in such an age of, we want things and we want things right now. So in, in the way of at least diabetes research, you know, it's, it's happening and it's good, but it, it just takes such a long time, which you obviously are very well aware.

Dr. Webber: 29:54

and I'm aware, and I appreciate the, the impatience of especially parents. You know, who want to see better technologies for their children, who they, they don't want to see suffering. They want to see have normal lives and be able to, you know, to do the things that, you know, other kids do without having to worry without the anxiety, without the constant decision making and monitoring and these kinds of things. And so, I mean, that's the reason we try to develop the technologies we develop. And I fully understand that people are impatient and they want these things yesterday. Right. And, and and that's, that's great. And I think. You know, I think, especially in a parents of diabetic children and especially the mothers of diabetic children are just a force of nature and they're just the most inspiring people. And how, when you think about it, you know, they call my office, they come see me. They, you know, they, they email me constantly, you know, wanting to know more about when these technologies are going to be available. When are we going to be able to help, you know, children and, you know, and I think, you know, they've done some of the greatest greatest work for, for type one diabetes, you know, In history, which is, you know, I mean the, you know, the two mothers who, who are the founders of JDRF, right? And like JDRF is a phenomenal organization that has done so much good for improving standard of care for, for diabetics. And so, you know, like I said, I, I appreciate how passionate are. I, I appreciate how impatient they are and certainly that motive that motivates, and that fuels our, our work as well.

Katie: 31:21

Yeah, I don't think I've ever heard anybody say thank you for being so impatient. I like that.

Dr. Webber: 31:27

Well, I mean, I it's awesome. It's great. I think, you know, I mean, I think this is what drives us, right? We know that there's a need out there that people want, and that fuels us to try to deliver those new technologies and those new solutions, right. For a problem that clearly exists and clearly has a, has a, a, you know, a large cohort of people that are, that are super passionate about seeing this.

Katie: 31:49

absolutely. We want the best for our kids. So thank you so much for the work that you're doing in your lab at Notre Dame. And thank you for again, taking the time to come on and talk to me today. I will leave a link in the show notes to where people can find out more about the research we're doing and kind of follow along as you guys progress.

Dr. Webber: 32:05

Yeah, I appreciate that. It's, you know, it's fantastic. Come here and talk with you. And I never turned down a chance to talk about our work because of. Because of how much I know that this, you know, the stuff we're doing means to people and also, you know, talking with you and we know, and meeting your listeners and other sorts of people really helps inspire the work we do. And I get to go back and tell the team about the people I meet and the stories I hear and you know, how the things they're doing are, you know, beyond just them in their thesis research or the next paper, they want to write that. We're really thinking about how we can bring something to fruition that. That could really have an impact in people's lives. And so I think that really adds meaning and adds value to the things we do for sure. And so I, I love having these kinds of conversations, so I appreciate the opportunity to take it, to talk about what we do.

Katie: 32:49

Yeah, I'm just curious. Does anybody on your team have type one diabetes?

Dr. Webber: 32:52

Yeah. I have one person on my team and I was type one diabetes. And you'd believe. He's one of my only ones that doesn't work on a diabetes relevant research project.

Katie: 33:00

Yeah.

Dr. Webber: 33:01

I, I gave, I gave him the option and he basically, you know, when he started and he said, you know, that's kind of like everyday life for me. And if you don't mind, I'd prefer to do something that wasn't, it wasn't so personal. And I said, yeah, then that's perfectly fine. And so so he's got a great project on. You know, materials that could that could be triggered in the presence of localized inflammation in the body and deliver drugs to localized areas of inflammation, which may be, would have a role in, you know, autoimmune types of diseases like diabetes, but maybe, you know, other things as well.

Katie: 33:32

what did you call it earlier? The it's the response like you're all of the things you're working on in your lab, type one, diabetes, diabetes related or not, they all have to do with sensor responses. What did you call it?

Dr. Webber: 33:44

Yeah, like stimuli, responsive materials is really sort of our interest. And so I'm, I'm bored by things that don't move. I'm bored by things that just stay static. And so I really like things that can undergo interesting changes as, or as a result of some stimulus. And so these are, are materials that have always just kind of excited me. How can we engineer things that can, that can have a communication with the living world can talk to things like blood glucose or to cytokines or to you know pH or other sorts of triggers that are relevant for different diseases. And how can we use those to then drive changes in materials in a way that would be responsive to those needs?

Katie: 34:21

Amazing. You guys are brilliant. I love it. thank you again, Dr. Webber, and I'll be definitely be keeping up with you. I'm interested to see where this goes.

Dr. Webber: 34:28

No. Thank you very much, Katie, for the chance to talk to you, it's been great to about our work, so I appreciate it

Katie: 34:34

Yeah, you're very welcome. You have a nice week.

Dr. Webber: 34:36

And DTS you as well.

Katie: 34:38

Thank you. And that's a wrap. You guys know what to do head on over to the show notes and look for all the links. I'll put a link to where you can learn more about what Dr. Weber in his team is doing over at Notre Dame. I'll put a link to the product feature of the week, those little four ounce plastic juice bottles, a link to buy me a coffee, if you want to support the show so I can keep bringing awesome content to you each and every week, and probably a link to something else. Just check it out. It'll be a surprise when you get there. I hope you guys had a great Thanksgiving. Thanksgiving was last week and I really hope you took the time to listen to diabetes, the musical. I hope that put a little pep in your step, this holiday season, and I hope you are going to be singing your way through the new year. All right guys, have a fabulous week and I'll talk with you soon. Bye.