Channel: European Association for the Study of Diabetes clear
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| 1 | European Association for the Study of Diabetes | EASD 2017 Immunomodulation - Chantal Mathieu, Matthias von Herrath and... | 429 | 4 | 44.5 | 12:19 | So now we'll talk about immunomodulation in type 1 diabetes. I'm here with Chantai Matieu from University of Løven. Matieu is from Herat, a professor and expert on type 1 diabetes and auto-cost green from University of Opsala. So where is the field currently and why haven't we cured type 1 diabetes yet? Well that's a question. I, as a clinician, very often get for my patients with type 1 diabetes and it's not because of lack of try. There's a lot of research on going worldwide, very high-level research and we are making progress. We are getting better insights into what is this disease that is type 1 diabetes and what we've learned is that it's really a very complex disease with not only what we taught a couple of years ago, the immune system just attacking the beta cell as a sitting duck and the beta cell dying. We've now also learned that the beta cell itself plays a very important role in its own destruction, sending out signals to the immune system and dying in a certain way. So it is a complex disease. Is it one disease? The diagnosis is made on just the clinical symptoms and it wouldn't surprise us as we gain more and more knowledge that we will be able to stratify these into multiple different diseases that end up with the same beta cell destruction and then the same clinical symptoms will develop. Certainly we need some form of stratification also for the trials. Because one thing that's slowing us down is that we have metabolic endpoints for the clinical trials and they often take some time and because also they heterogeneity in disease progression pathology, I'm not sure yet, but heterogeneity in disease progression that drives up the amount of patients you have to enroll for each arm and then the trials become long, complex and very costly and that's of course not accelerating things. But Chantal, we mentioned it, we're making progress. Absolutely, absolutely. But about the heterogeneity, again for the clinicians it's so obvious that a child who gets type 1 diabetes at two years of age is very different from the person getting it at 40 years of age. And as Mathia said, biomarkers, biomarkers that would allow us to better phenotype, characterize patients in order to get, if we get interesting tools to intervene, to give the right tools to the right patient and also to design better trials. And so there are many efforts on going, on finding better biomarkers and yeah, understanding this disease better. In a way it's an exciting time because now we have these big consortia like I am, I am an odia and so forth, like trial net where everybody begins to work together. And I think for finding proper biomarkers and dealing with large cohorts of people, that's absolutely needed, that's not a single lab or person's effort. And in a way it's an exciting time and an exciting time of progress. Yeah, and what is important is if we want to beat this beast, if we want to prevent or cure this disease, we will all have to work together. Not only academics, but also industry. And as Mathia said, in initiatives like in odia supported by IMI, you have the funders, you have the academics, you have industry and patients. Everybody working together, trying to get a better idea of how this disease is going and how can we really do something. But I think one of the biggest challenges we already said heterogeneity biomarkers, but another big challenge to me is the fact that we have no access to the organ where everything is happening. And as for instance, Ola has demonstrated, this is really very important because a lot is happening in the pancreas. And I would say also that the field is benefiting now of the technical development in parallel to the diabetes research. So imaging biomarkers, everything like that is also very interesting period in time now. Development is really, really fast in those areas. And my hope for the very near future is that these technologies will give us tools to stratify people and to bring into clinical trial, but also to help us in designing good endpoints of our trials. And of course in respect to the pathology, it would be really nice in a way if one of these days we understand what causes this disease. And as Chantal and Ola already referred to, it's complicated. We just now with access to the human organs begin to understand that's an interplay between beta cells and their immune system most likely, but there has to be also other factors, maybe environmental factors. We don't know them. We have a struck empty finding a virus that causes the disease that was a popular hypothesis over many years. And they have been these hygiene hypothesis, but we also have struck empty to identify a single culprit, but we need to look more because as there's no in feeling, I think you have this too that we might overlook something. You have brought forth interesting hypothesis about the pathogenesis. I think the field needs this to be a bit shaken up to make us think again. And maybe if we have the cure, if we have the cost then finding a cure for the disease will become easier, right? I think also that the type one like this is an orphan disease in the way that it's one of the most severe chronic disease a young person can be affected by. But in terms of funding, attention in the general public in our society, it's much, much inferior when compared to cancer or other diseases that also affect young people. So I think also we need to get an increased awareness of how promising the research are and that we actually are going hopefully to be able to treat our patients much, much better in the very near future and perhaps also cure the disease in some people affected. Interesting trials are running. I mean we are doing trials, but as Matthias said there's always this challenge of getting homogeneous group of patients to really be able to make solid conclusions and refute certain therapies. I think we've made some mistakes in the past like with the anti-CDT where we took very heterogeneous populations took very strange endpoints. So trials that are running now are typically trying to combine certain therapies. Therapists that might protect the bed ourselves together with immune modulation for instance and we try to get better, more solid endpoints that make more sense in preventing or arresting a disease like type one diabetes. It's absurd that you would have as an endpoint hemoglobin A1C in these days where you have analogue pumps and what have you. You know this is trying to arrest an autoimmune destruction of the beta cell. So we need to have markers of beta cell function or a beta cell mass that are really the endpoints and so a lot of effort is put into also convince regulators for instance to accept these endpoints in a disease like type one diabetes for instance CPAP type and that's not obvious it's very different from type two diabetes. And also one big problem in doing clinical trials is that by tradition the regulatory bodies in our countries often only accept one investigational drug to be tested and what Chantal is talking about is that we take home a sit from the entire field now is that we have to combine different treatment options. And where do you time the trials like at what stage of the disease or the patient? That's that's a very crucial question and relates a little bit to the issue what do patients really need and how much are they willing in a sense to pay or take in terms of side effects for them. That's one way why we need these combinations maybe to have more synergies with two different therapies but spread the side effects so the therapy becomes more palatable for the patients and we can also if we're talking about prevention then of course the benefit for the patient could be greater because you could stave off the disease for several years and there's little argument that that of course is a very strong benefit especially if you're talking recent on such trials there's now pumps there's better means to control glycemia there's sensors so the incentive for the patient to do something drastic becomes lower and the bar for the therapy in terms of no having no side effects and achieving lots becomes ever higher if climbing sort of in front of us and we would also like to salute all the patient participating in different tries. There is this altruistic attitude in the community so we can ask patients to participate in the trial that just would generate knowledge they would not benefit from being part of the trial but they are willing to participate just to help us to help other people affected even if they because individual cannot. Exactly and again also you know these patients are so supportive of all our initiatives and they help us to better understand this heterogeneity to develop better biomarkers another challenge is that very often we are dealing with children and also the first degree relatives of these children are children and so we they are so motivated to give their blood and other samples over and over again so indeed it is very important but then again it comes to Matias' comment about the bar we are treating children so side effects safety it is really a very big discussion when you think on the one hand we're trying to arrest all gym union destruction of the beta cell or improve the beta cell function but on the other hand we are treating young people for a long period of time and you know finding the right balance between efficacy and and safety and acceptance of side effects is what makes this also difficult. Yep and that translates to the timelines because often you have to test something in adults first if it can be done and I think that's fair so that takes longer before you can move it down the line in age to three and so the overall tries timelines to finding a new drug candidate and then having a face one safety and a face two maybe ideally combination that's like five years maybe if you're really lucky for the new candidate two years for the safety and some biomarkers maybe another trial for face two with more biomarkers so you're already a decade out and you're in the best case done with a face two trial whether you have to then take a step back and say does this qualify for face three it's it's not so fast for the right reasons I mean because of children being affected and because of safety but that was your initial question and of course the question from all the patients. Well thank you very much for participating in this discussion. Thank you. | ↗ |