Heiko Lickert and Carolin Daniel are researchers of the Helmholtz Diabetes Center at Helmholtz Munich.
While Heiko focuses on diabetes and regeneration research,
Carolin conducts her studies in the area of immunological tolerance in diabetes.
Hundred years of insulin in diabetology have changed the lives of millions. Since the first treatment, researchers have learnt a lot about this vital hormone. Will we ever be able to cure diabetes?
Carolin: It is our great goal that one day no child will have to be newly diagnosed with type 1 diabetes. Population-wide testing will be of key importance to achieve this goal. It will help to detect children at risk of developing type 1 diabetes or with an early stage of the disease. This will improve disease management and the opportunity to develop and efficiently apply prevention strategies including insulin-specific immunotherapy. Recent clinical trials employing immunotherapies to restore beta cell function and to prevent or delay progression to clinical type 1 diabetes showed some promising successes. We are very excited that these immunotherapies are getting closer to their expected approval by regulatory authorities.
Heiko: Currently, all drugs on the market treat the symptoms of diabetes (meaning high blood sugar levels), but not the root causes which is beta cell loss and failure. Thus, to stop the steady increase of the number of patients we see an urgent medical need for pharmacotherapies that can protect or regenerate endogenous beta cell mass or function. Two promising approaches include triggering endogenous beta cell regeneration and replacing lost cells by human pluripotent stem cell-derived beta cells. In both cases, research is giving extremely promising successes.
Insulin is crucial or even lifesaving for many diabetes patients today. However, the injections come with side effects. How do you envision the treatment of insulin-dependent patients in the future?
Heiko: Insulin has been used as a treatment for almost 100 years, but the increased risk of unintended weight gain (hypoglycemia) and the existence or development of insulin autoantibodies limit the broader use of insulin also as a preventive drug. Islet transplantation has been successful in terms of restoring normal blood sugar in type 1 diabetes patients. However, it requires immunosuppression to prevent allograft rejection and is limited due to the lack of donor organs. This is why we need novel therapies to protect or regenerate the functional beta cell mass and stop the disease progression. In combination with single-cell-omics, bioinformatics and AI analyses, we identify novel targets for regenerative therapy. Recently, we have identified a novel and druggable insulin inhibitory receptor, named inceptor. Blocking the function of inceptor increases the sensitisation of insulin signalling and thus protects pancreatic beta cells from failure. The clinical translation of these findings might allow to protect and/or regenerate beta cells for the prevention or remission of diabetes.
Carolin: Additionally, it is important to consider that besides its life-saving role, insulin is also the primary target of the autoimmune reaction in type 1 diabetes. This insight can be used to develop future insulin-specific immune intervention strategies. Such strategies include innovative approaches of immunotherapy using insulin to habituate the body to the hormone and novel vaccines based on mRNAs to train the immune system. Additional opportunities might evolve from combining insulin-specific immunotherapy with other immune-adapting agents.
Diabetes already has an epidemic dimension with rising numbers. Nevertheless, its urgency is not omnipresent. What can we learn from the current COVID-19 pandemic?
Carolin: The global challenge of COVID-19 clearly showed that if public, politics, pharmaceutical industry, and the research community are pulling together we are able to make considerable progress and even reach scientific breakthroughs in a very limited amount of time. Such an impressive progress could also be possible for diseases like diabetes if we see them as the global threat that they are and increase our joint efforts accordingly.
Heiko: Currently, 463 million people worldwide suffer from diabetes; more than 7 million just in Germany. Every seven seconds a person dies of diabetes. None of the current pharmacological treatments can stop the progression of the disease or prevent the development of more or less severe complications that can lead to premature death. The COVID-19 pandemic has put us in front of an important challenge and has shown us that by making an incredible effort all together, in a short time you can reach life-changing scientific results. This is what drives us.
Listen to Helmholtz Munich researchers talking about their research in the detektor.fm podcast “Forschungsquartett”: 100 Jahre Insulin – Neue Wege gegen Diabetes (available in German only)
Ziegler et al., 2021: 100 Years of Insulin: Lifesaver, immune target, and potential remedy for prevention. Med, DOI: 10.1016/j.medj.2021.08.003
Siehler, Blöchinger, et al., 2021: Engineering islets from stem cells for advanced therapies of diabetes. Nature Reviews Drug Discovery, DOI: 10.1038/s41573-021-00262-w