INSIDE OUR LABS: TREG THERAPY AND OTHER AUTOIMMUNE THERAPIES
Fact: Type 1 Diabetes (T1D) results from the autoimmune destruction of insulin producing pancreatic β-cells by cells in the immune system. β-cell loss becomes virtually complete over time and leads to lifelong dependence on insulin injections. Immune-based therapies that target these destructive immune cells have been attempted with promising results, however, disease prevention and lasting diabetes reversal remain to be achieved. Therefore, new strategies able to create more lasting effects are critically needed and need to incorporate not only inhibiting the destructive immune responses, but also stimulate immune regulation and promote β-cell health.
Allison Bayer is a Research Assistant Professor in the Department of Microbiology and Immunology at the Diabetes Research Institute, University of Miami School of Medicine. Her lab focuses on Treg therapy and other autoimmune therapies. The main overarching goal of their current work is to better understand autoimmune-targeted treatments and how it can lead to diabetes reversal or late-stage development treatment. They focus on understanding the mechanisms by which the immune system provides immune regulation to maintain health and prevent disease, often characterized as immunological tolerance.
Dr. Bayer is currently working on two projects: “Dimethyl fumarate (DMF) as novel agent for autoimmune diabetes” and “Antigen-specific Treg Therapy for Islet Autoimmunity”, which are both in preclinical stages.
The DMF project was started after FDA approval for its usage in the treatment of multiple sclerosis in nonhuman models. Data from this project showed that DMF targets innate and adaptive immune response by metabolic inhibition from downregulating aerobic glycolysis. This resulted in a decrease of TH1 and TH17 cells and an increase in anti-inflammatory TH2 subsets, Treg cells, and CD56bright NK cells.
The second project focuses on increasing the clinical feasibility of Treg therapy. Current trials are at a standstill due to the inability to generate enough cells for the inhibition of desired immune responses. To overcome this, other labs are working on expanding populations of Tregs, but Dr. Bayer’s project is focused on understanding the desired environment needed for long-term stability. A recent paper from her lab demonstrates approaches utilizing anti-CD3 and antigen-specific Tregs to treat long-term autoimmune diabetes without the need for immunosuppression . Understanding the needs for an optimal environment and overcoming the need to take immune suppressors are two major requirements for success in Treg therapies, and this must be met in order to have a successful clinical trial .
Both projects can heavily impact how autoimmune diabetes is treated in the late stages of diabetes development and onset. The DMF project will hopefully lead to a treatment for islet autoimmunity which in turn can lead to an approach that maintains endogenous insulin secretion. Additionally, this work strives to improve Treg engraftment by ensuring an ideal environment after islet transplantation takes to treat diabetes. Furthermore, Treg therapy also seeks to cure diabetes by preventing beta cell destruction.
Why is this research and that of the DRI so promising? In the last 10 years, great strides continue to be achieved to better understand the disease pathologies in T1D. We are now starting to observe immunotherapies in the clinical setting that are beginning to show a clinical impact in delaying the onset of T1D, but currently fail to establish long-term tolerance. It is time that combination approaches are to be seriously considered as accruing data demonstrate that single agents cannot on their own achieve the long-wanted objective of suppressing the autoimmunity underlying T1D. To continue down this pathway to a biological cure for T1D, more in-depth knowledge of how immune-based therapies effect immune microenvironment in a curative manner are still needed to develop more comprehensive approaches to cure T1D. To gain this understanding and to strengthen the DRI’s research endeavors, the newest and latest technologies need to be employed.
Research summary written by Alex Parrot, The (Sugar) Science
- Faleo, G., Fotino, C., Bocca, N., Molano, R. D., Zahr-Akrawi, E., Molina, J., Villate, S., Umland, O., Skyler, J. S., Bayer, A. L., Ricordi, C., & Pileggi, A. (2012). Prevention of autoimmune diabetes and induction of β-cell proliferation in NOD mice by hyperbaric oxygen therapy. Diabetes, 61(7), 1769–1778. https://doi.org/10.2337/db11-0516