(left to right) Qian Liu, MD, assistant professor, Department of Medicine, UMDNJ-New Jersey Medical School (NJMS); William C. Gause, PhD, University Professor of Medicine and Senior Associate Dean of Research, NJMS; David Bleich, MD, associate professor, Department of Medicine, and director, Division of Endocrinology, Diabetes and Metabolism, NJMS
Preventing Type 1 Diabetes with Helminthic Parasites
any attempts have been made to understand why northern latitude countries like Finland have dramatically higher rates of type 1 diabetes (up to 55 per 100,000
population) compared to equatorial countries like Venezuela and Peru (0.1 to 0.5 per 100,000 population). This 100- to 500-fold worldwide difference in the incidence of type 1 diabetes is thought to be due to unknown environmental factors that inhibit the disease by interacting with the immune system. Studies in twins also confirm a major role for environmental factors in type 1 diabetes, whereby the concordance rate of type 1 diabetes in identical twins is 30 to 40 percent, suggesting that at least 60 percent of the disease is attributable to non-genetic, environmental factors.
Recent studies suggest that infection with parasites can influence the immune response, inducing regulatory cell populations that control the development of inflammatory diseases, including type 1 diabetes. One hypothesis proposes that the eradication of certain environmental pathogens (e.g. parasites) in Western society leads to an imbalanced immune system that can contribute to the development of type 1 diabetes and other immune-mediated diseases in susceptible individuals. In fact, epidemiological studies have determined that the rate of autoimmune diseases like multiple sclerosis, Crohn’s disease, and type 1 diabetes have increased about 4% annually over the last 30 years due to environmental effects.
In the Center for Immunity and Inflammation at New Jersey Medical School, we have undertaken a collaborative research effort to understand the relationship between parasite helminthic infection and type 1 diabetes. This project builds on my expertise in type 1 diabetes and the expertise in studies of the immune response to intestinal parasite infection of Dr. William C. Gause, Senior Associate Dean of Research, and Dr. Qian Liu, assistant professor in the Department of Medicine. Together, we have established a model of parasitic infection in the non-obese diabetic (NOD) mouse, a strain that closely mimics human type 1 diabetes by developing spontaneous insulin-requiring diabetes at 12 to 30 weeks of age.
Previous studies by the Gause laboratory using a helminthic parasite called Heligmosomoides Polygyrus (Hp) demonstrated that this infectious agent generated a highly polarized type of immune response that is associated with elevations in cytokines and regulatory cell populations known to down regulate the inflammatory responses associated with certain autoimmune diseases, including type 1 diabetes. Generally, the immune system is comprised of a balance between Th1-type responses (characterized by the production of the cytokines interleukin-12 and interferon-Y) that lead to pro-inflammatory, immune conditions and Th2-type responses (interleukin-4 and interleukin-13) that can counteract these inflammatory effects.
Our recent studies have demonstrated that treatment of NOD mice with the gastrointestinal parasite, Hp, led to prevention of type 1 diabetes compared to untreated NOD mice that develop diabetes 90 to 100 percent of the time by 30 weeks of age. Moreover, Hp infection was capable of generating the predicted Th2 immune response without causing harm to the infected NOD mice. In fact, our Hp-treated NOD mouse colony has thrived for up to 40 weeks without any evidence of adverse side effects and without evidence of type 1 diabetes.
Our short-term goal in this project is to fully characterize the alterations in the immune response when NOD mice are infected with Hp. We anticipate that this characterization will provide us with important information about how to block immune-mediated type 1 diabetes in human beings. Our long-term goal is to implement human studies with helminthic infection to assess the impact of such therapy on type 1 diabetes. Already, human beings with Crohn’s disease have been treated with the parasite Trichiuris suis (Ts) to determine whether this agent can ameliorate disease activity in those patients refractory to other forms of therapy, and significant improvement in the severity of Crohn’s disease was observed (Science 2004. 305:170-171). These and other studies raise hope that parasitic infection or specific parasitic products will one day be a viable therapy in immune-mediated diseases including type 1 diabetes.
The funding for this project was provided by the Foundation for Diabetes Research of New Jersey.
David Bleich earned his MD from New York Medical College in 1983 and completed his internship in internal medicine at Maimonides Medical College in 1984 and his residency in internal medicine at Maimonides in 1986. He did a fellowship in endocrinology and diabetes at Brigham and Women’s Hospital, Harvard Medical College, from 1987 to 1990. He is board certified in endocrinology,
diabetes and metabolism as well as internal medicine. He is an associate professor of medicine and director, Division of Endocrinology, Diabetes and Metabolism at UMDNJ-New Jersey Medical School.