Using the JAK1/JAK2 Inhibitor Baricitinib to treat new-onset Type 1 diabetes

Summary The goal of this project is to investigate whether the JAK inhibitor baricitinib dampens autoimmunity and preserves beta cell function in human type 1 diabetes.

Project Details

Our goal is to prevent the immune-mediated destruction of insulin-producing pancreatic beta cells that leads to type 1 diabetes. The JAK-STAT signalling pathway is critical for immune-mediated pancreatic beta cell destruction. We have shown that inhibitors of JAK1/JAK2 prevent diabetes and also reverse newly diagnosed diabetes in the non-obese diabetic (NOD) mouse model of type 1 diabetes. The goal of this project is to investigate whether the JAK inhibitor baricitinib dampens autoimmunity and preserves beta cell function in human type 1 diabetes.

We plan to conduct a placebo-controlled trial to investigate the safety and efficacy of baricitinib in 83 individuals aged 12-30 years with recent-onset type 1 diabetes. The primary objective is to determine if baricitinib can reduce the loss of meal-stimulated C-peptide, a measure of beta-cell function. As exploratory objectives, we plan to evaluate the impact of baricitinib on type 1 diabetes-associated immune responses. To achieve this, we will use two complementary approaches, single-cell proteomics and single-cell transcriptomics. We hypothesise that baricitinib will induce intra-individual and inter-individual changes in immune cells. Single-cell RNA-seq will capture the biological pathways altered by baricitinib while mass cytometry will be used to capture the phenotypical and functional differences between cells.