Dual-action approach targeting inflammation shows potential as Type 1 diabetes treatment

Type 1 diabetes is a lifelong condition in which the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. The loss of these cells leads to high blood sugar levels and requires ongoing insulin therapy and careful monitoring to avoid severe health complications.

In laboratory studies using human cells and mouse models, the researchers found that applying a molecular method to block inflammation signaling through the tyrosine kinase 2 (TYK2) protein reduced harmful inflammation in the pancreas. This strategy not only protected the beta cells in the pancreas but also reduced the immune system's attack on those cells. A medication that inhibits TYK2 is already approved for the treatment of psoriasis, an autoimmune condition that causes skin inflammation.

"Our study showed that targeting TYK2 could be a powerful way to protect insulin-producing beta cells while calming inflammation in the immune system at the same time," said Carmella Evans-Molina, MD, PhD, co-author of the study and director of the Indiana Diabetes Research Center and the Eli Lilly and Company Professor of Pediatric Diabetes at the IU School of Medicine. "This finding is exciting because there is already a drug on the market that does this for psoriasis, which could help us move more quickly toward testing it for Type 1 diabetes."

Past genetic studies have already shown that people with naturally lower TYK2 activity are less likely to develop Type 1 diabetes, further supporting the group's approach for future treatments using this TYK2 inhibitor approach.

"Our preclinical models suggest that the treatment might work in people as well," said Farooq Syed, PhD, lead author of the study and assistant professor in the Department of Diabetes-Immunology at the Arthur-Riggs Diabetes and Metabolic Research Institute of the City of Hope. "The next step is to initiate translational studies to evaluate the impact of TYK2 inhibition alone or in combination with other already approved drugs in individuals at-risk or with recent onset Type 1 diabetes."

Syed conducted the research while working in the Evans-Molina lab at the Center for Diabetes and Metabolic Diseases and the Herman B Wells Center for Pediatric Research at the IU School of Medicine. The Evans-Molina lab partnered on this study with Decio Eizirik, MD, PhD, a professor at the Université Libre de Bruxelles Center for Diabetes Research and other international collaborators. The research team hopes their findings will support future clinical trials to safely assess the efficacy of a new drug or drug combination in humans.

Additional IU study authors include Chih-Chun Lee, Jyoti Rana, Preethi Krishnan, Staci A. Weaver, Garrick Chang, Namratha Shivani Chalasani, Kara Orr and Jamie L. Felton. Other study authors include Olivia Ballew, Stephane Demine and Donalyn Scheuner from the Indiana Biosciences Research Institute; Angela Castela, Maria Ines Alvelos and Alexandra Coomans de Brachène of the ULB Center for Diabetes Research; Sofia F. Thomaidou and Arnaud Zaldumbide of Leiden University Medical Center; Lorella Marselli and Piero Marchetti of University of Pisa; and Jing Liu of Purdue University.