As the primary organization in the United States serving all people with diabetes, ADA’s Research Programs invest in projects that have the potential to help people with type 1 and type 2 diabetes. Projects include strategies to address complications of diabetes or restore proper insulin production. For specific examples of projects currently funded by the ADA, see below.
Laura Cristina Alonso, MD
University of Massachusetts Medical School
Project: T2D risk-SNPs at the CDKN2AB locus
“Regenerating beta cells may seem like a reach-for-the-stars kind of goal today, but to me it seems like the best way to really get to the bottom of the problem, for good. We hope these experiments, which we are performing entirely in human beta cells, will one day guide design of new medicines that regenerate beta cells to prevent or treat diabetes. This is an important goal not just for type 1 diabetes but also for type 2 diabetes.”
The problem: More than 100 different genes have been identified that increase risk for type 2 diabetes (T2D). However, for most of these genes, we don’t understand why they alter risk. In order to personalize therapies, we need a better understanding of how certain genes affect diabetes risk.
The project: Dr. Alonso is studying one of the genes that impacts risk for developing diabetes. Her initial findings indicate that insulin-producing beta-cells from patients containing risk variants in this gene have more difficulty replicating, potentially resulting in fewer beta-cells and less insulin secretion. Dr. Alonso and her team are now doing experiments to figure out the molecular mechanisms underlying this reduced replication potential in beta-cells from people with a diabetes risk variant in this gene.
The potential outcome: If successful, these studies will give a lot more information about how one region of the human genome contributes to diabetes risk. Additionally, it has the potential to lead to novel ways to expand the number of insulin-producing beta-cells, a potential treatment option for both type 1 and type 2 diabetes.
Wei Li, PhD
University of Miami School of Medicine
Project: A novel disease-selective therapy for diabetic retinopathy
“The results from this study will be used to support a clinical trial application to the U.S. Food and Drug Administration. Therefore, this award will support a translational research that may lead to a new drug therapy to treat diabetic eye disease.”
The problem: Diabetes can cause blood vessel damage in the eye, called diabetic retinopathy, which can lead to vision loss and blindness. Approximately 100 million people worldwide suffer from diabetic retinopathy. Therapies exist to treat diabetic retinopathy, but unfortunately, they impact both pathological and normal processes, and therefore are suboptimal.
The project: Dr. Li and his team have recently identified a molecule which is involved in pathological aspects of diabetic blood vessels but does not impact normal aspects of eye biology. This molecule is therefore a viable candidate to target in order to improve outcomes related to diabetic retinopathy. A medication to inhibit this molecule has been developed and tested in animal models with high efficacy and safety. The goal of this project is to further investigate this diabetes-selective therapy and to humanize the drug for clinical translation.
The potential outcome: This project has the potential to reduce the progression of vision loss in people with diabetes and to improve quality of life.
Juan Dominguez-Bendala
University of Miami School of Medicine, Diabetes Research Institute
Project: Pancreatic beta cell regeneration through ALK3 receptor targeting
“I have met and advised countless parents of children with type 1 diabetes, many of whom visit us often in the lab. This disease also afflicts some of my best friends. So, from a personal standpoint, this is much more than cells, DNA and exciting scientific innovations. The disease has very real faces and contributing to its eradication is a very powerful motivation. This award will be instrumental in helping us achieve that goal.”
The problem: The restoration of insulin-producing beta-cells is of paramount importance in the development of any effective therapy for type 1, as well as in some cases of type 2 diabetes. Cell therapies such as islet transplantation have been successful at correcting diabetes, and stem cell-based therapies are in the pipeline. Achieving the same result through pharmacological means (i.e., via a therapeutic drug regimen) would be especially interesting due to their faster track to clinical applications. However, no such therapies exist currently.
The project: Dr. Dominguez-Bendala is currently working to develop a therapy that will increase the number of insulin-producing beta-cells. He has shown that certain molecules can induce the formation of new insulin-producing beta cells in diabetic mice. In this proposal, he and his team of researchers aim confirming these results using a variety of rodent and human tissue models, an important step to the translation of these therapies to the clinic.
The potential outcome: If successful, this research will further our knowledge on human beta cell regeneration while speeding up the development of potential therapies for both type 1 and type 2 diabetes.
