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Detecting and preventing juvenile diabetes
By the time a child shows obvious symptoms of type 1 diabetes, 80 percent of his or her pancreatic beta cells — critical to producing insulin — are already destroyed or damaged by the autoimmune response directed against them. And as of now, there is no cure.
“When they come into clinic and they’re diagnosed the disease is practically over. What you’re looking at is the aftermath,” explains Martin Hessner, PhD, director of the Max McGee National Research Center for Juvenile Diabetes at Children’s Wisconsin. “And so it’s very important that we continue to focus on the interplay of genetic and environmental factors that contribute to type 1 diabetes. Understanding the mechanisms of this disease is critical to development of treatments aimed at delaying or preventing onset in those at risk and better treating those with diabetes.”
Dr. Hessner’s team developed a novel, cutting-edge blood test that can detect inflammation associated with type 1 diabetes up to seven years before the disease’s onset — and that also has implications for a host of other autoimmune diseases. The research was supported by funding from the Juvenile Diabetes Research Foundation, American Diabetes Association and National Institutes of Health, as well as endowed funding from Children’s Wisconsin.
Diabetes is a difficult disease to study because the relevant tissues, the pancreatic islets, are not accessible for biopsies. Autoimmunity continues through a long, silent preclinical period, but until recently, researchers didn’t have technology sensitive enough to detect the key immune signaling molecules related to this inflammatory state unless they were in very high concentration.
The solution: reporter cells from a healthy donor that serve as the “canary in the coal mine.” When incubated with plasma from a patient who has inflammation, the healthy reporter cells are activated. Researchers then study their response by using a microarray, a technology that can measure activity levels for 50,000 genes at once. The readout, a “signature” of regulated genes unique to type 1 diabetes, is evident years before the patient shows clinical symptoms and offers important insight into the pathways responsible for the disease.
In collaboration with researchers in Europe, Dr. Hessner’s group has used the novel assay to study patients undergoing a new anti-inflammatory therapeutic intervention for type 1 diabetes. The approach was able to identify those responding to treatment from those who are not. Dr. Hessner’s group has also collaborated with investigators at the Medical College of Wisconsin to compare diabetes’ genetic signature to other disorders, including cystic fibrosis, bacterial pneumonia, H1N1 influenza, multiple sclerosis, Crohn’s disease, sickle cell disease, and cancer.
“Remarkably, in each case the observed signature was disease-specific,” he says. “Overall, these studies validate the remarkable capacity of reporter cells to serve as disease-specific biosensors, capable of sensitively and comprehensively capturing the plasticity of the immune system and differentiating the diverse range of inflammatory processes that underlie human disease.”
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