Harmonized biomarkers to measure response to ustekinumab in type 1 diabetes

In type 1 diabetes (T1D), immune cells called T cells destroy insulin-producing beta cells, causing lifelong insulin dependence. Blood glucose control remains imperfect despite insulin injections, leading to an increased risk of complications from chronic hyperglycemia and a shortened lifespan. An antibody known as ustekinumab has been found to inhibit inflammation and can be safely administered to young adults with recent-onset T1D.

Our clinical trial, UST1D2, aims to test ustekinumab’s ability to halt progression of recent-onset T1D in young adults using patient samples collected from the BC Diabetes Clinic and the Mount Sinai Hospital in Toronto. This drug was previously demonstrated to decrease inflammatory proteins thought to damage beta cells, IFN-γ and IL- 17. Changes in inflammatory proteins and in the balance of immunoregulatory versus inflammatory cells may elucidate ustekinumab’s mechanism of action and biomarkers of response to therapy. The mechanistic studies will be conducted in Dr. Megan Levings’s lab at BC Children’s Hospital Research Institute, with Dana Lao, a Master of Science student at the University of British Columbia, acting as the lead trainee for the project.

To comprehensively evaluate mechanism and response biomarkers, the mechanistic studies carried out are harmonized between UST1D2 and another study called USTEKID that tests ustekinumab in children. This increases sample size, allowing for faster determination of treatment effectiveness. Our project contributes toward evaluating ustekinumab as a treatment for T1D patients and represents a new collaborative model to evaluate outcomes from international, multi-centre clinical trials.

This project is supported by the CANTRAIN-CTTP & Michael Smith Health Research BC 2024 Masters’ Studentship co-funded by the Canadian Consortium of Clinical Trial Training Platform (CANTRAIN) and Michael Smith Health Research BC.