Research Projects - Dr. Andrew Muir

Research Projects (Andrew Muir, MD)

Title: Phase II Multiple Dose Treatment of Type 1 Diabetes Mellitus with hOKT3?1 (Ala-Ala) (ITN027AI)

Nicknamed “AbATE”, this 2-arm, randomized trial of a “humanized” monoclonal antibody that binds the CD3 surface molecule on T-lymphocytes will determine whether the course of newly diagnosed type 1 diabetes can be altered. Emory will be one of five US centers that will recruit a total of 81 subjects who are willing to be randomized to either receive two 14-day courses of study medication or be followed with no treatment. Two subjects will receive medication for every one subject that is followed without treatment. The first course of medication will be started within 8 weeks of diagnosis and the second course will be given a year later. The primary outcome is the insulin (C-peptide) response to a standardized mixed meal. Preliminary studies have demonstrated that a single course of medication can transiently preserve pancreatic beta cell function. This trial will determine whether the benefit can be prolonged with a second course of treatment.

Title: Prospective Assessment in Newborns of Diabetes Autoimmunity (PANDA)

Originally designed to trace the natural history of islet autoimmunity in children with a genetic predisposition to type 1 diabetes, the study has evolved into a search for improved diagnostic measures and an improved understanding of the pathogenesis of “pre-diabetic” autoimmunity and chronic complications of type 1 diabetes. Relatives of patients with type1 diabetes are first screened for genetic risk and autoantibody markers of autoimmunity. Immune cells from high-risk non-diabetic subjects are studied for changes in immune responses compared to healthy controls and overtly diabetic patients. Methods include immune cell function assays as well as high throughput genomic and proteomic studies. In addition, well-characterized, overtly diabetic subjects provide urine and blood samples to allow a search for early changes associated with chronic complications of diabetes.

Title: The Environmental Determinants of Diabetes in the Young (TEDDY)

This study was spawned by PANDA and other similar studies. It is an international collaboration that focuses on genetic predisposition, environmental exposures, and genetic-environmental interactions that are associated with the initiation and perpetuation of autoimmunity against pancreatic beta cells. A number or environmental exposures have been implicated in the pathogenesis of type 1 diabetes, but no prospective studies have yet been attempted. Two cohorts of newborns will be monitored in TEDDY for fifteen years: 1) those with affected first degree relatives and no protective genotype and 2) those with no affected relatives and a high-risk genotype. Extensive characterization of exposures to breast milk, macronutrients, micronutrients, medications, immunizations, infections, psychological stress will be accompanied by serial sampling of blood and other biological samples. Using a nested case-control design, associations between environmental exposures and beta cell autoimmunity will be sought. In addition, interactions between exposures and genes known to influence the course of beta cell autoimmunity will be sought. Three centers in the US and three European centers (Finland, Sweden, Germany) are collaborating on this long-term project.