I am involved in a variety of different translational and clinical research projects, most related to diabetes. A number of the on-going studies are attempts to alter the course of autoimmune-mediated type 1 diabetes, often via immunomodulation, in order to preserve endogenous beta cell function. Some of the recent and on-going projects are described below.
Most of this work occurs in multi-center clinical trials. I am the Clinical Center director for the NIH sponsored program TrialNet, a multi-center research consortium that develops trials to delay or prevent the onset of type 1 diabetes in those at risk, or prolong endogenous insulin secretion (the honeymoon phase) in those with new onset disease. UCSF is one of 14 national centers for this 7-year study. Current studies include:
-natural history study to screen and predict who might develop type 1 diabetes
-a prevention trial with omega 3 fatty acids to determine if treatment during pregnancy or shortly after birth can serve as a primary means to prevent type 1 diabetes
-a new onset diabetes trial with mycophenolate mofetil with our without IL-2 receptor monoclonal antibody to determine if this will preserve endogenous insulin secretion
-a new onset study with anti-CD20 monoclonal antibody to determine if this will preserve endogenous insulin secretion
The consortium is continuing to develop additional prevention and new onset studies over time.
In addition, I have served as the site director for a novel study evaluating the role of an anti-CD3 monoclonal antibody in prolonging the honeymoon phase in those with new onset type 1 diabetes. The initial phase 1 / 2 study results were published in the N Engl J Med 2002, and our 2 year follow-up data was just published (Diabetes 2005). These exciting results were confirmed in an independent study with a related drug in Europe, and have spawned a series of studies to build on these initial findings. We are now launching an NIH-sponsored phase 2 study for new onset diabetes, evaluating the efficacy of antibody treatment every 12 months for 2 courses. In addition to these efforts, we have several additional NIH-funded new onset type 1 diabetes studies that will soon begin. We are evaluating the window of opportunity for anti-CD3 therapy, with a trial planned for subjects from 4 to 12 months from diagnosis. We are developing clinical trials the assess the effect of anti-CD3 therapy coupled with antigen, and another study coupling with an incretin hormone analgoue, exenatide, which may help with beta cell regeneration. Finally, I am the study principal investigator for a multi-center new onset type 1 diabetes trial with anti-thymocyte globulin, sponsored by the Immune Tolerance Network.
I am partnering with other members of the UCSF Diabetes Center to pursue other clinical trials, and translational studies that may help us better understand the pathogenesis of type 1 diabetes. Such studies include development of T cell assays; characterization of patients with novel disorders in carbohydrate metabolism; possible use of T regulatory cells as an immunotherapy. As technology advances, we anticipate to one day be able to use beta cells developed from stem cells as a definitive treatment for type 1 diabetes.