[vc_row][vc_column][vc_column_text][/vc_column_text][/vc_column][/vc_row][vc_row][vc_column][vc_column_text]For the first time, researchers have managed to delay the onset of type 1 diabetes. In a breakthrough study, TrialNet was able to delay the onset by two years.
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Stacey talks to Dr. Michael Haller in-depth about this and other studies. An excerpt of this interview ran in our previous episode. In this episode you'll learn more about how TrialNet works, other promising studies and why it's so difficult to prevent an auto-immune disease. Plus, an update on the funding for TrialNet and why they've changed how they re-screen families and individuals.
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Episode Transcription below
Stacey Simms
Dr. Haller. Thanks so much for joining me, exciting times. I'm really excited to talk to you today.
Dr. Michael Haller
My pleasure to be here.
Stacey Simms
Before we get into the prevention studies that came out and other things that are going on, let's really kind of dial back and start at the beginning. Can you tell me a little bit about what TrialNet is and what you're trying to do?
Dr. Michael Haller
Sure. TrialNet is an NIH funded consortium of the top type 1 diabetes centers across the US and Canada and even Europe and Australia. And our goal is to try and develop therapies to ultimately prevent and reverse diabetes. And to achieve that goal, we have to identify patients who are either newly diagnosed with type 1 so we can encourage them to participate in research studies, trying new drugs to see if we can protect the remaining beta cells extend their honeymoon phase and hopefully eventually get to reverse their disease. And then the bigger chunk of what that does is actually tries to identify folks who are at high risk for developing type 1 diabetes by screening family members of people who are already affected with type 1 to see they have markers of autoimmunity, and then either follow them to see if they progress to being higher risk, or put them in prevention trials aimed at trying to delay their disease.
That’s really the main emphasis of TrialNet that it's a huge operation. As you can imagine, trying to identify people who are at risk for type one is not easy, because people don't walk around with a name tag on that says, “Hi, my name is Mike, I'm at risk for type one.” We have to draw the blood and identify markers in their blood and we have to talk people through why they would want to do that. So it's an exciting time for all those efforts. But it's certainly a big challenge.
I'm going to skip around here a little bit. So forgive me if, as you listen, this sounds out of order, but I have to jump ahead because the news came really recently that we had the first study to show that any drug can delay type 1 diabetes, the diagnosis. Can you talk to us about this?
It's called teplizumab. It's a mouthful. Teplizumab is a monoclonal antibody designed to track the parts of the immune system to knock out or kill cells that have a marker on them called CD three. And CD three is sort of like a name tag for these kinds of cells that are going out and attacking the pancreas. Now, unfortunately, it's not so specific that it only attacks those cells that might be targeted at the pancreas. You know, there's some collateral damage that it gets rid of other cells that are part of the immune system, but that's the big challenge in in type one is trying to find drugs that can get rid of the silos that we want to get rid of and not and not the ones we want to keep.
But the results of this study are really, truly exciting and paradigm shifting for the field. As you mentioned, this is the first time in the history of type one that we've been able to show that anything can really durably delay or prevent the disease from progressing. So what that study did was take patients like I mentioned, who are high risk for developing type one, so family members of somebody who has type one who had markers in their bloodstream that told us they were going to progress to clinical disease where they need to take insulin in the next several years. And they were treated with this, this drugs immunomodulatory drug teplizumab. And what the data have now shown, the paper was recently published in the New England Journal of Medicine, was that in fact, the drug did delay onset of type one, which means there was actual prevention and some of the patients on average for at least two years, and so while it's certainly not a home run, we can't guarantee that we're preventing the disease forever and the patients who received the active drug versus who received the placebo agent. It's a huge win for the field of type one, it establishes the proof of concept that we really can effectively change the natural history of the disease. And I hope that it accelerates our efforts to do more and more studies with other drugs like teplizumab and adding additional agents to try to get an even better effect for our patients so that we can ultimately say, hey, it makes sense to screen everybody for their risk for type one, sort of a public health initiative and treat them with these drugs to prevent them from getting the disease.
Something I've always wondered. And I don't know if you can answer this. Why is it so difficult to prevent or treat autoimmune conditions? It's not just type one, right? I mean, nobody's cured or really prevented an autoimmune disease, have they?
Dr. Michael Haller
Yeah, it is a challenging beast. You know, the immune system is really smart, even when it's confused about what supposed to do. And so once the immune system has decided it wants to attack cells tissues, which is what we mean by auto immune disease, and then type one, we just are specifically looking at the immune system attacking beta cells. It figures out all kinds of different pathways to get to that end, and cleverly changes the way it does it. And so it’s probably not surprising that it's been so challenging, just given the way autoimmune diseases in general come about and specifically help type one happens.
And in the type one space, we're further challenged by the fact, and so it's a good challenge in the sense that we've gotten better, better caring for diabetes. So you know, people reasonably would say, I don't want to take a therapy that's a risky agent or drug to prevent or reverse the disease because I can potentially take care of diabetes with insulin and pumps and continuous glucose monitors.
Now, I don't live with diabetes personally, but you know, I have a personal connection to it. My grandfather had type one and I take care of patients every day. And while I understand that argument, but the majority of my patients I talked to say and I had currently understand that living with type one is incredibly challenging and hard and, and more patients than not are actually willing to accept a little bit of risk for the potential benefit of delaying that disease. And certainly a two year delay for most families who've now lived through this is would be tremendous. And most folks who have gone through that would say, “Man, if I could have just gotten my kid from six to eight, or eight to 10, or 10, to 12, or any amount of time, Some even say a day would be worth it.” That'd be totally fine.
Stacey Simms
Personally, my son was diagnosed right before he turned two. And I got to tell you from almost two to almost four, I take that in a heartbeat because he could not even say diabetes when he was diagnosed. Yeah, I mean, the communication was not there. I mean, it's unbelievable at that tiny little age to get them to tell you what's going on. But let me ask you about the people in the study. Do you mind sharing a little bit about but how does it work? My hat is off to anybody who takes part in any kind of clinical trial, whether it's technology or drugs or medications, these, these are pioneers and people who are sacrificing even if they may say otherwise. You know, they're taking time, they're taking risks. So my hat is way off. But can you tell us a little bit about what kind of goes on during something like this?
Dr. Michael Haller
Sure. And thank you for bringing it up yet to patients who participate in these studies are absolutely the diabetes heroes. Sadly, not enough patients are able to participate in studies just because of the time commitments and logistics and maybe being risk averse like you mentioned. So if you know somebody who participated in a study, please give them a hug and a high five and a hearty thank you. Because without those folks, we can't find these things that might work and move the field forward.
Stacey Simms
Let’s start with the study. Say I'm a mom, I've got a six year old or whatever the age of the person is here. I don't know how much detail you can share or what might be interesting, but I've never participated in something like this. So I show up at TrialNet. Then what do I do?
Dr. Michael Haller
The trial starts with a screening study. We just draw some blood from somebody who's got a first degree relative or a secondary relative with Type 1 diabetes. And if the markers in their blood show they have the antibodies that we associate with risk for type one, then we asked them to come back for additional testing. And the frequency of that testing is dependent on what we learn about their risk from the next set of tests. And so for patients who are particularly high risk, which is the kind of patient who was enrolled in the lab study, if they were old enough to be in the study, and they had the right risk markers, which included completing an oral glucose tolerance test that was already abnormal, but not quite at the diabetes diagnostic level. So these were patients who are really unfortunately, high risk really on the verge of getting diabetes within the next few years. They were offered the opportunity to participate in this trial.
And when you when you mentioned that it's a big commitment, teplizumab is not an easy drug to receive. It required a 14 day infusion of the drug as an IV. So every single day for two weeks, patients had to come in and get poked and get an infusion which was technically a half hour infusion. But by the time you come and get your IV placed and get the drug and follow up, we're talking about several hours every day for two weeks. So huge commitment. But nevertheless, if I told you that those two weeks was going to buy you a two year window or potentially longer of diabetes free time, I don't know many patients or families that wouldn't say sign me up. I think it is a paradigm shifting thing. We just, we hadn't had something that did this before. And now that we do, I hope that it will encourage more and more families to participate in the research process to sign up for screening to hopefully find other therapies like teplizumab to find out how we can improve on teplizumab’s findings and so that we can ultimately tell patients one day that you know, we're screening your kid, not just for research, but because we know we can do something about it.
Stacey Simms
What's next for teplizumab. Is this study kind of done? Do you now start something new to see if you can prevent it longer? What happens next?
Dr. Michael Haller
Yeah, a little bit of both. We obviously met the study’s primary endpoint and published those data. But now there are lots of questions to ask and answer, which is how long does it benefit last and those who got treated? And what happens if we retreat? Some of those patients who got drug appear to be responders and still haven't developed type one? Can we extend the benefit even longer if we give them another course of the drug? And so TrialNet is actively looking at those options right now. I think one of the challenges for teplizumab and specifically is it's a, not an FDA approved drug for anything at this point. It's still been even though had a long history of being developed for this purpose and being tested in the type one space multiple times in new onsets and now in this prevention space, it's never been licensed. So despite the excitement about it, you can't just go out and get this today from your endocrinologist or anybody else. The only way to get it would be through a study so the company that owns it is trying to do new and additional studies both in newly diagnosed patients. In fact, they just opened up a study. That's not part of trial that but it's by the company, and then TrialNet is going to be doing some version of the either a retreatment study for treatment with teplizumab plus other agents is likely to come down the road because we all still believe given to early question about the complexity of autoimmunity, that we're going to have to do more than just a single drug to kind of get us over the end zone, we're probably going to require combination therapies or what we call induction and maintenance therapy. So first treating with teplizumab and then some other drug to keep the effect going.
Stacey Simms
Another recently completed study, my understanding is, ATG-GCSF, can you talk us through a little bit of what that one is?
Dr. Michael Haller
Sure. So the study of thymoglobulin (ATG) and GCSF which stands for granulocyte colony stimulating factor – I apologize for all the letters and names - has been a labor of love and a passion of mine personally for the last decade or so. The work that came out of that really is a beautiful example of the importance of translational science that came out of my institution of the University of Florida.
The story is really interesting. There was a transplant immunologist, who was using fairly aggressive what’s called non- myeloablative transplant approaches for people with really severe bad autoimmune diseases like end stage rheumatoid arthritis and multiple sclerosis. And he was having really impressive outcomes. But his approach was really quite aggressive. It would be akin to almost doing chemo therapeutic treatment for these patients. And so he started to talk about the potential of using that approach in type 1 diabetes. And honestly, the US type one community just wasn't willing to think about that because the risk level was was so much higher and we hadn't really had any successes yet. So we ultimately took that approach to a group in Brazil and and did new Patients with this approach to their and today is still probably the most potent way to provide a short term reversal of Type 1 diabetes that we've seen in newly diagnosed patients. And so our group was really interested in that.
But before we really have to dissect this, take it apart, deconstruct it and try to put it back together in a way that would make sense for treating kids and a US audience because of the risk there was just too high. And so we went from the bedside, essentially back to the bench and we started doing animal studies in the mouse model type one, and found that two of the drugs that they use in this sort of very complicated approach really gave us the most bang for a buck and those two drugs were ATG and GCSF. And so once we had demonstrated that repeatedly in the animals, we decided we would do a pilot study in humans.
And the first thing we did was actually study this and folks who had what we call established type 1 diabetes, people who had diabetes for at least four months, but as long as two years because that population often largely has been ignored in the timeline. intervention space, even though we now know that many of those patients have lots of beta cell function still around. And what we were able to show was that the combination provided for almost a 40% preservation of their ability to make beta cells and start to make insulin alpha two years after a two day treatment of a anti thymocyte globulin and a 12 week course of the GCs F. So that was really exciting. But we wanted to then continue to move it sort of earlier in the disease process to new onset and ultimately, into the prevention space. So at that point, we convinced the TrialNet and the NIH to fund a large confirmatory study, similar to this episode we just talked about, but a new onsets to see if the low dose of ATG with or without the GCSF, could provide protection for beta cell function and improve A1C. And we've now published one year and more recently, two year data. And in fact, we we didn't show that so the most interesting finding was perhaps that the the low dose of ATG by itself was able to provide for the most robust preservation of beta cell function and reduction of hemoglobin agency and newly diagnosed patients.
Why I'm really excited about this approach is it sort of related to what we just talked about before with teplizumab in that entire time aside, globulin is been around for 25 years. It's a commonly used medicine in hospitals every day. It's primarily used for pre treatment of folks getting kidney transplants, but in that indication, they use it at a 10 times higher dose. So we're using it as a very minimal dose of this drug. And we still need to do more studies to confirm our observations, but the pathway to taking it into the clinical care of patients is perhaps a little bit more direct, because it's been around and already has a label.
Now, of course, we'd have to do additional studies to get a label for the type one space. And you know, that's being considered right now, but, but I'm excited about the opportunity to continue to study ATG, I think it's very similar to pull them out in many ways. It has some advantages and that only requires a two day infusion. Instead of a 14 day one. And so the next step is for trial maps to start a prevention study and that study is being planned as we speak. That would be very similar to the teplizumab study that we talked about taking high risk patients, giving them a low dose of HCG. And following them to see, in fact, that can prevent them from progressing to clinical diabetes where they need insulin.
Stacey Simms
So exciting. And you mentioned people with type one who are not newly diagnosed. Let's just talk about that for a moment. Because I agree, I think there's a feeling that well, these prevention studies are fabulous. And you know, one day, we'll make sure that, you know, no one develops type one, but what about the people who do have it? Were you surprised? Or I guess I should ask you put that in perspective for us that discovery that they're still producing beta cells that something can still be done here.
Dr. Michael Haller
Yeah, a lot of people don't realize that. But I think one of the best ways to think about it was analogy that previous director of the JDRF made, which was, if you think about an hour of the clock as being the amount of time somebody lives with Type 1 diabetes, the new onset phase, which is the first hundred days, where we've normally done these studies, is like less than a minute. And so we ignore the whole rest of the population who live with type one, many of whom fund our research through, you know, being donors or advocates, we sort of leave them out of the opportunity to participate. So one that's wrong morally and two it's wrong, because we now have better science that demonstrates that people with type one, especially those who were diagnosed a little older, unfortunately, not kids, like your son who were diagnosed so young. But people who are diagnosed as teens or even young adults, often have functional data cell mass for years, even five to 10 years is not uncommon, and it's quite variable, but we can measure that and know and those patients are potentially huge population who might benefit from some of these immunotherapies that we're talking about. So I think you're starting to see the pharmaceutical companies And the scientists who work with these drugs, designed trials to sort of re-infranchise that population that's long been left out. So we felt that that was very exciting and important finding from our study, our first study of ATG and GCSF. And now we are seeing other studies like it coming along.
Stacey Simms
Alright, so let's just go backwards for a moment and talk about people diagnosed very young, like my son who was diagnosed at 23 months. I hate to hear something like that. But I have to ask, Can you elaborate on what you meant by that? Nature has no real cut offs, but you know, what, what ages are you talking about there?
Dr. Michael Haller
Yeah, so unfortunately, kids who are diagnosed under four to five years of age tend to have a more rapid and severe disease in that their beta cell mass is, is less when they're diagnosed, and they just may retain less over a shorter period of time. And it's a little bit obvious that you know, somebody who made it to 30 or 40 or 50 years of age before they developed type one, obviously had a slower progression of disease. So in some sense, it's not too surprising that their progression after the day they need insulin is going to be slower than in somebody who unfortunately, developed type one at 23 months. But as you can imagine, it's incredibly variable.
It's one of the challenges of type one, there's so many flavors of type ones. And every individual patient is different, you know, I haven't done this now for 20 years, I still every time I walk into a patient's room, you know, their diabetes is different than the patient I saw before and will be different the patient I see next. And that's probably true for some of the biology of what's going on with the immune attack. And so it's probably not a one size fits all, won't be a one size fits all approach. And we have to get better at personalized medicine. So know what wait what may work as a therapy to prevent diabetes in a 10 or 15 year old, or even a 30 or 40 year old is going to be different ultimately, then what will likely work for somebody who's you know, a year or two old and really high risk.
Stacey Simms
It's really interesting. I mean, I as a mom, you know, I just pointed I don't want to hear things like that. But for the purpose of the interview here the information, it's really interesting and it kind of explains Benny my son had basically no honeymoon once he was diagnosed and we were very fortunate he wasn't in DKA It was not an emergency situation that day, but boom that was it. We never looking back we never had a honeymoon period.
Dr. Michael Haller
Yeah, that’s a pretty common experience. Unfortunately for kids diagnosed that young. They just, you know, they just trashed their beta cell mass so quickly that they don't get a honeymoon. Yeah.
Stacey Simms
That's a great way to put it. My son will be thrilled to know that he totally leveled it.
Dr. Michael Haller
He killed it. He knocked it out of the park, not the game you want to win unfortunately, but you mentioned something else. So that's really a key factor which is that he fortunately didn't develop DKA but still even in the US 30 to 40% of new onsets come in in DKA And sadly, that number continues to go up, not down. It's another really critical reason to do screening programs. You know, while we can't yet justified general global screening For the purposes of preventing DKA, people who have a family history of type one certainly should get screened in TrialNet and be followed because we know, very good data that folks who are followed in these studies have a marked reduction in the likelihood of DKA for a subsequent family member who unfortunately, might be developing type one. And so while you know, economically, it doesn't make sense, you know, obviously, no parent who's gone through this would say that they wouldn't do something to prevent DKA and another child who might have to deal with it. And we're talking about a reduction from, you know, 30 to 40%, which we're seeing in the general community down to the 5% or less. So that's a huge secondary benefit of participating in these trials.
Stacey Simms
You know, one thing that has come up recently, though, unfortunately, and as you say, you want to do more screening, but TrialNet seems to have had the funding cut back. Can you talk a little bit about the changes that have come? Because I did get when I told people we were going to be talking about prevention, and I was speaking to TrialNet I heard from a few people who said ask them how long the changes are going to go on.
Dr. Michael Haller
I appreciate you asking that question. And for all your listeners, we appreciate your ongoing advocacy Keep, keep speaking up being loud about the value you find in these programs and talk to, you know, your congressmen and senators. Ultimately, that's where the money comes from town that is funded by the National Institutes of Health. And we get a bit of a special allocation of my own money called this special diabetes project. SDP monies, unfortunately, looks like it's going to move forward with some some newer funding. But yes, we did recently face some budgetary cuts because of decisions that had to be made at the at the NIH level. And because of that, we had to strategically talk about how much screening we could do to still identify the highest risk patients that we need to put in these prevention trials. And part of that calculus resulted in us having to cut back on the frequency with which we had previously been doing repeat screenings, but I completely agree with all the you know, upset families out there part of that huge value of being part of our family was Being able to come back in for rescreening every year. And either knowing that your kid wasn't that increased risk this year, or finding out that unfortunately, they were but knowing that, therefore, that that meant you would get a closer follow up and intentionally be in a prevention trial. So I remain hopeful that that decision will be overturned, to be short lived. But at the end of the day, it's a purely economic one. And so, if any of your listeners have influence or everybody can, you know, don't be shy about giving that feedback to your TrialNet center if you're already in TrialNet or talking to your legislators about why you think this is important.
Stacey Simms
We have international listeners as because TrialNet is not just in the US are these are these funding issues in like the UK as well?
Dr. Michael Haller
Thanks for bringing that up too. So TrialNet it is mostly funded by the NIH but we also get some funding in kind from the JDRF and the direct funding has largely been used in the past. To help us maintain the international centers. And so, you know, they as a group, given that we use the funding all the same, are affected in the same way as it relates to this current screening change, because we can't have a different program in different countries. But again, hopefully as funds will come back to the network, we will be having the ability to increase our screening programs. And I should say, some of the screening things need to be changed anyway, because the network is evolving, and we're learning more and we have better more precise ways of doing things. But you know, some of some of the changes that were made were, were certainly a little bit more draconian than we had hoped.
Stacey Simms
Let's talk if we could about some other prevention theories. As you can imagine, with the podcast, I get a lot of interesting guest pitches and emails. And when I'm very careful, you know, I have a no snake oil policy, and we try to do a lot of research before we let things through. But one of the things that comes up time and time again, our stories about people who are diagnosed with Type 1 diabetes, but prevent the onset or extend the honeymoon by diet. Is that possible?
Dr. Michael Haller
The short answer is, it doesn't appear that that's possible. We don't have any evidence that supports that assertion. The longer answer is certainly if you, you know, restrict carbohydrates, which obviously was the way we treated diabetes before we had insulin, you essentially went on a starvation diet, and that will no doubt reduce the severity of the hyperglycemia. But it doesn't ultimately change the beta self destructive process. And unfortunately, before insulin was discovered, you know, this was a uniformly fatal diagnosis. So there are a lot of people who are very interested in excited by using diet as part of the therapy for type one and I absolutely agree that is an important part of what we do eat everything has a huge effect on glycemic load. But diet and of itself is unlikely to be able to change the immunology and the natural history of the beta cell loss. And there really isn't any data to support that of yet.
Stacey Simms
Anything else with prevention. I mean, Verapamil is not a prevention drug, right? It's not with those trials, or is it?
Dr. Michael Haller
It hasn't gone into prevention trials yet. But sure, there's tons of things on the list that we'd like to continue to try out. And honestly, the main limitation, to do all those things is an adequate number of people identified and willing to participate in the studies in a trial that screens 20 to 25,000 people a year, but when even if you're screening, first degree relatives, only one in 20 are going to have antibodies. And so you know, as opposed to one in 300 in the general population who are at risk for type one, so it takes a lot of work to identify a high risk patient and then, you know, they may not want to participate in the study again, The particular agent’s risk profile or the logistics or any number of reasons. So again, we really need people to participate in screening because we have lots of drugs that we'd like to try.
Verapamil is a very interesting drug that is an old blood pressure medication. And a recent publication demonstrated it may have the capacity to preserve beta cell function as well in new onsets .It's a relatively small trial in adults that needs to be repeated in children and adults. And then if those results are confirmed, it would absolutely make a lot of sense to us in prevention or combined with another agent. So again, we talked about, you know, maybe teplizumab plus other drugs or ATG plus other drugs, Verapamil would certainly be on the list, but I should mention that TrialNet is already planning additional prevention studies as well. So we have we have an an open trial that's a mechanistic based study. So it's really not designed to answer the question of whether or not a drug this particular drug can prevent disease, but it's designed to give us some scientific answers to questions that if they look good would would lead to a larger trial.
And that's using actually an old, more anti malarial drug called hydroxychloroquine. And then there's another drug that's being evaluated for a trial as well. That's a really interesting story. It's called methyldopa. Methyldopa is a really old blood pressure medication, and through some really beautiful science. And that drug was found to bind to a particular area that really is critical in the way our immune system sees insulin and might develop an immune response to it. So this is sort of a backwards way of discovering an old drug in a new way, by screening entire libraries of agents to try to find things that fit into particular areas of a part of the immune system. And so that's that is also being planned. So we have a lot of things in the pipeline. There's a whole number of other autoimmune drugs that are used for treating things like you know, arthritis and psoriasis, and the list goes on and on that we'd love to repurpose to see if they might work well in type one. But to do those things we need patients, families willing to pay it. And of course, we need funding.
Stacey Simms
You mentioned that your grandfather had type 1 diabetes. What do you remember about that? Would you mind sharing his story a bit?
Dr. Michael Haller
Sure. Yeah, so I'm not terribly old. I guess it's all relative. I'm in my 40s. But I remember even as a young kid, when we essentially had to influence and that's what grandpa took. And I remember very vividly when the first blood glucose meters came out. And I have sort of some memories of when he was still using cleany test tabs for any of your old timers out there. When we were before we had the glucose testing. You sort of did a chemistry experiment in the bathroom with your urine to see what your blood glucose might have been four hours ago, to think of that where we were and again, thinking I'm not all that old of the guy to where we are now. It's just miraculous how much type one care has improved. I mean, you know, to think that continuous glucose monitor Essentially standard of care now that we have multiple insulin analogs, and you know that we have insulin pumps that are now talking to those CGM and the potential for sending closed loop systems is almost realized, is just amazing and miraculous. And my grandfather lived into his 80s. Even with old school influence, and all those things, because he lived a incredibly regimented life, he was really good at exercising every day and eat his very similar meals. And he was essentially a good patient, and did the best you could do with what the technology was. And so I use his experiences with living with type one to hopefully motivate my patients, remind them, essentially, that diabetes is always going to be a terrible disease until we can prevent and reverse it, but but if you had to choose a time to living with it, you know, now it's not so bad compared to what it used to be like. And now the pace of improvement is just accelerating so nicely that even a year goes by and we we discover and improve things better than the last 10 years. So I think the future looks very bright.
Stacey Simms
I'm always astonished to hear if people who lived well, at a time before you mentioned all these great technological advances, but who lived before home glucose meters, the idea of not being able to check your blood sugar even two times a day? Or, you know, did you have to, as you said, the tabs and you know, the urine kits, and it's amazing to me, that must have been such a sea change for people like your grandfather, with his diagnosis, does that mean that you can participate in trial that can be considered enough.
Dr. Michael Haller
So I would be a second degree relative as a grandchild. And now I'm unfortunately above the age limit, you have to be 21 and a second degree relative to be screened. But I've been involved in the TrialNet and before that was the diabetes prevention trial that I did get screened back when I was very first starting out in this because I've been fortunate enough to work with Dr. Desmond Schatz, who's a world renowned pediatric endocrinologist was a previous president of the American Diabetes Association, but I've worked with him since I was a teenager Actually, that's my first experience and really working in type one was working in his lab back on the first trial designed to see if we could prevent type one using oral insulin. And that was called the diabetes prevention trial type one. So back then I did get screened. Unfortunately, I didn't have antibodies and I was old enough at that point, even though I was still a kid to not really need to be re screened.
Stacey Simms
That's fascinating. So in high school, you knew this was going to be your life was that because of your grandfather? What made you want to go into endocrinology?
Dr. Michael Haller
Yeah, I I totally knew I was pre med. And I had that experience of seeing my grandfather. But honestly, it was it was more of a mentoring opportunity than anything else. That's just such a wonderful person to work with. really got me passionate interested about the field. And then I went off, I left. I grew up here in Gainesville, Florida, where the interest in Florida is, but I actually went to Duke University for undergraduate school. But when I graduated, and it was time to make my decision for medical school, Dr. Schatz was again, extremely influential, and he really is what convinced me to come back to Gainesville, do medical school here and then residency in pediatrics, and then along The way I started participating in diabetes camps. And that was really what did it the combination of being able to work in a field where I could do some really interesting science, take care of patients long term. And frankly, go to go to diabetes camp, which was just such an amazing experience, made it very clear to me that I should be a pediatric endocrinologist.
Stacey Simms
Do you still see patients?
Dr. Michael Haller
Oh, yeah, no, I do. I'm a little bit of a strange breed in that. I always have seen myself as a clinician who happens to do research. And so while I don't get to do clinic every day, cuz I have so much research and administrative responsibility now, I would never give that up. And, you know, most of the research I do is is really patient oriented research. And in fact, I get the pleasure of being able to spend more time with my research patients just because it's not under the same guys as a clinic where you have to see a patient every 40 minutes or hour. So everything I do is is really patient base, but I work with an incredible team of scientists, and so I get to work with Mark Atkinson and Todd brosco and Clive waterfall and clay Matthews and an up and coming scientists who, who do a lot of the work in the lab, and then bring us these great ideas to try to test and patients so that we have a really unique team here at the University of Florida that allows us to do those things.
Stacey Simms
Is it difficult to see patients who are kids, I mean, my son has a great relationship, his endocrinologist, we've been able to see the same one. Luckily, from ages two to now he's 14. And I wonder, Is it difficult to know that you're researching, you're, you know, you're trying to do prevention and, you know, which hopefully even someday cure, but you're, the research is slow. I mean, and and we understand why it's not a criticism, but the research is slow, and the patients are growing up, is it difficult and any kind of emotional level to look at your patients and feel like, gosh, I really want to help these people more. Uh, but you know, the research just isn't as fast as we would like it to be.
Dr. Michael Haller
It's so incredibly frustrating. It frankly it pisses me off, but part of why I get up every morning. come to work and I'm excited to move things forward. I mean, the pace of research is glacially slow. And I'm not a patient guy. So I've lost my cool more than one time trying to promote what I think is important research so that we can get these things to our patients faster. And that's why I mentioned I think, like a clinical guy just happened to the research, because at the end of the day, that's what pulled me into research, I realized that was what we had to do to get the patients better care. So yeah, I find the process, you know, it's necessary. It's what we have to do, we have to do good science, and that takes time. But sometimes the administrative burdens or the funding lags those things can just be so mind numbingly frustrating that, you know, really good people, unfortunately, sometimes leave the field. And so we I would encourage people not to do that, of course, we need people to stay passionate about type one and do the hard work of the research and the clinical care. But yeah, I have to go to clinic and look people in the eye and say, Sorry, I don't have anything that's good enough for you yet. And I emphasize it yet. But that's a hard conversation to have with people day in day out.
Stacey Simms
I'm glad I asked. I wasn't sure that that question was going to go anywhere. Yes, sometimes people look at me like, I'm crazy when I asked things like that.
Dr. Michael Haller
no, it's not crazy at all. And it's just part of why I'm excited about the entire time. It's like globulin, and ultimately, CD three and all these other things. Because, you know, we're getting so much closer to the point where I can really say to somebody who's been newly diagnosed, I have something I can actually do for you. And this may no longer be just a research question. And they'll always be research questions, because we can improve on things, but I may have a real therapy besides but we've been doing now for close to 100 years, which is just just give you insulin. Obviously we're better at doing that too. But it sure would be nice to do something besides that.
Stacey Simms
Sure, would you you did mention the oral insulin study. My ears perked up on that. Is that complete? What happened with that?
Dr. Michael Haller
Yeah. That's a good example of this challenge we have between risk and benefit. So for a long time, we've wanted therapies and the type one space that would be entirely without risk in Orleans one. It was one of those a pill that you take by mouth, obviously orally, but doesn't affect your blood glucose. And it's essentially an immune tolerating therapy, at least that's the idea to convince the immune system to recognize insulin that gets sort of chewed up in your stomach as a as as being you and therefore not not attack it. And the reason the rationale for this studies were that when you give oral insulin to a particular type of mouse that gets diabetes, it's very effective at preventing them from getting diabetes. And so everybody was really excited about it. And so one of the first large scale multicenter trials designed around the attempt to prevent type one was the diabetes prevention trial I mentioned and that was the precursor to what became TrialNet. And that trial, unfortunately, didn't demonstrate a benefit, although there were some signals that were, you know, suggested that there might have been benefit in certain subpopulations. And so tronics subsequently did a, again, a large trial of oral insulin in that particular population that looked like it might benefit and sadly that to fails. Demonstrate benefit. And so, you know, I think what that demonstrates is type one's really hard to fix. And to that animal models don't always tell us the whole story. In fact, they often tell us the wrong story, but we're stuck using what we got to get some idea of proof of concept. And then lastly, that we are going to likely need to use things that have more potency, that are a little bit more, you know, side effect profile associated to be able to really change the needle on where diabetes is going. That's not to say that oral insulin may not still have some potential for benefit. In fact, we've never tested it when we've given it after something like Simon globulin or to Lizzie Mab or in combination with other immunomodulatory modulatory therapy. So there may still be life for Orland Flynn or other antigens specific therapies. And there are many others that are that are sort of in line for testing as well. But that story is, you know, almost 15 years or more of effort, and just again, exemplified how long it takes to find out the real answer. We all want answers quickly. But if we don't do the science the right way, we continue to promote bad ideas and in hearsay, and that's just not how we're gonna get get real therapy that benefits patients.
Stacey Simms
You know, Mike, we've talked a lot about, you know, exciting studies and some setbacks and how long things take and the frustration, are you still jumping out of bed excited to do this research?
Dr. Michael Haller
Now more than ever, I mean, it's a really exciting time to be here, because we now have stuff that looks like it actually works. I mean, the feeling in the room in the last decade when we kept going to meetings and reporting negative events, was certainly weighing on everybody heavily. And so to be able to come to the American Diabetes Association and report these data nationally, internationally in the last couple years with the outcomes like Simon globulin and and CD three, really has been a huge boost everybody's morale and I think puts us in a really great space because we can continue to argue that people should be getting screen we should be doing these studies. Because we are effectively changing the Natural History of the disease. So I'm really excited about where we're going. And I just hope we can get there faster.
Stacey Simms
Wow. Well, Mike, thank you so much for joining me. We'll put all the information about TrialNet in the show notes so that people can learn more and find out how to get screened on but I really appreciate that. Thank you so much for joining me today.
Dr. Michael Haller
That's been my absolute pleasure.
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