The JAK-STAT signalling pathway is critical for immune-mediated pancreatic beta cell destruction. We have shown that inhibitors of JAK1/JAK2 prevent and reverse diabetes in the non-obese diabetic mouse model of type 1 diabetes. Our BANDIT clinical trial is testing the JAK inhibitor baricitinib in new-onset type 1 diabetes. We have collected blood samples throughout the trial to evaluate the impact of baricitinib on type 1 diabetes associated immune responses. We will use multiple approaches, including flow cytometry, to analyse changes in immune cell populations and single cell RNA sequencing to document molecular changes that occur in response to baricitinib.
The goal of these studies is to identify ways to measure disease activity. Unlike other autoimmune diseases, there are no clinical features in type 1 diabetes that indicate disease activity. If successful, the BANDIT trial will be followed by other trials using JAK inhibitors and by trials of other immune therapies. This research will lead to a better understanding of type 1 diabetes pathogenesis and contribute to design of these other trials.