The research group of HSC's Dr. Michael Dosch traced the link between Type 1 diabetes and nervous system autoimmunity to nervous tissue surrounding insulin-producing beta cells in the pancreas. They unexpectedly found that it is these nervous system structures that are first destroyed in the earliest stages of diabetes, with autoimmunity subsequently veering off to attack insulin-producing cells. Modification of the early nervous tissue attack prevented subsequent diabetes in the major animal model for the disease.
"This study maps the puzzling link between Type 1 diabetes and nervous system autoimmunity," said Dr. Dosch, the study's principal investigator, an HSC senior scientist and a professor of Paediatrics and Immunology at U of T. "In focusing previous research efforts strictly on insulin-producing beta cells, we may have missed the start of the diabetes process in its early, perhaps earliest, stages. The new data may shed a different light on the process, providing new targets for preventive treatments and new, early markers for the detection of disease risk, a prerequisite for intervention treatments."
Dr. Dosch's research group used a vaccine-type approach to alter autoimmunity against the pancreatic nervous system cells in mice, and they observed that subsequent diabetes development was reduced by a large margin. This implied a critical role of early neuronal autoimmunity in the process that eventually leads to beta cell destruction and then to diabetes.
The research team included co-lead authors Shawn Winer and Hubert Tsui, PhD students at U of T, Dr. Pamela Ohashi from the Ontario Cancer Institute, Dr. Pere Santamaria at the University of Calgary, and Dr. Dorothy Becker, University of Pittsburgh. The group also collaborated with SYNoX Pharma, a Toronto proteomics research and development company, to first identify and develop diagnostic tests. These are based on the SYNoX discovery that the early phase of autoimmune attack leaves traces (protein markers) that can be detected in blood. Work in Dr. Dosch's lab, in collaborating labs in Europe and the US, and at SYNoX, is focused on refining the detection of these traces into lab tests that may possibly diagnose diabetes risk much earlier than is presently possible.
"SYNoX's unique Proteomics Discovery Platform
"This research may also open a new door for understanding the persistent mystery in autoimmune diseases: why does the immune system attack its own tissue? It now seems possible that the nervous system and cells that separate nervous system from other tissue in the body may play an unsuspected, critical role in this process," added Dr. Dosch.
This research was supported by the Canadian Institutes of Health Research, the National Institutes of Health (US), the Renziehausen Fund, and The Hospital for Sick Children Foundation.
The Hospital for Sick Children, affiliated with the University of Toronto, is Canada's most research-intensive hospital and the largest centre dedicated to improving children's health in the country. Its mission is to provide the best in family-centred, compassionate care, to lead in scientific and clinical advancement, and to prepare the next generation of leaders in child health. For more information, please visit www.sickkids.ca .
Nature Medicine