Title of Project:
The interruption of beta cell autoimmunity and
the restoration of beta cell function of type I diabetes

 Principal Investigator: Denise Faustman, MD, PhD.
Associate Professor of Medicine, Harvard Medical School, and
Director of the Immunobiology Laboratory of Mass General Hospital Diabetes Unit.

 Abstract:

This innovative research project will study both mouse and human subjects with type I diabetes.  The three-year study will be conducted at the Massachusetts General Hospital (MGH), aimed at developing a cure for human type I diabetes, based on the success of new therapy in diabetic mice.  Dr. Faustman’s team discovered a novel and safe treatment program that permanently cured 75% of diabetic mice.  The six weeks course of treatment that cured the mice consisted of two new drugs that were able to locate and destroy a specific defective type of immune cell.  This defective immune cell, called a naïve T cell, stop the mouse’s insulin producing cells from producing insulin.  Most humans have type I diabetes for this very same reason-defective immune cells stop insulin producing cells from working.  The cure not only permanently eliminated the disease-causing immune cells; it caused the dormant insulin-producing cells to begin producing normal amounts of insulin in response to blood sugar!

The researchers believe that this diabetic mouse treatment can cure human Type I diabetes.  A three-part program of research is proposed:  Project 1 involves studies to identify changes needed to safely and effectively use this treatment in human type I diabetics, including finding a replacement for the second of the two drugs that restore the diabetic to health.  The second drug works well in the mice, but is unsuitable for human use.  This portion of Project 1 is the research that can be supported by the Brinson Foundation grant.  Project 2 develops a test to measure the amount of defective immune cells in blood samples from type I diabetics.  The test will allow researchers to take blood from type I diabetics and confirm that they have a treatable defect.  It will also reveal how well the therapy is working.  Project 3 will enroll 40 patient volunteers into a Phase I study to check their response to the first component of the two- drug protocol. 

The studies proposed have two overall goals.  The primary goal is to refine, optimize and then adapt the therapy shown to cure diabetes in the NOD mouse to the human type I diabetic.  The second goal is to establish and validate a new set of tests that can detect different levels of defective immune cell, and which can be used both for patient selection for clinical trials, and to monitor the success of therapy in real time.  There currently are no automated tests of immune system activity.  These tests will be essential for all future trials in type I diabetics.  In addition, this therapy could lead to treatments for other autoimmune diseases such as lupus and ALS.

This research program is directed by two internationally recognized leaders in diabetes laboratory-based and clinical research.  Dr. Denise Faustman, Associate Professor of Medicine at Harvard Medical School and Director of the Immunobiology Laboratory of the MGH Diabetes Unit, is Principal Investigator of Projects 1 and 2.  Dr. David Nathan, Professor of Medicine at Harvard Medical School and Director of the General Clinical Research Center and the Diabetes Clinical Research Center at the MGH is the Principal Investigator of Project 3 and co-PI of Project 2.