Dextran Sulfate, Beta Cell Preservation, and Immune Regulation in Type 1 Diabetes
Abstract
Type 1 diabetes (T1D), with a prevalence of ~200/100,000 and an incidence that has been increasing by 2%-5% worldwide over the past few years, poses a considerable challenge to afflicted individuals, to the development of effective prevention and treatment regimens, and to public health initiatives at large. The U.S. Department of Veterans Affairs has recently reported that nearly 24% who served their country have diabetes. Data from the period 1997 to 2007 indicate that 6% of diabetes diagnoses in the military were T1D. This indicates that a large number of Veterans have T1D with a significant healthcare cost associated to it. In T1D, the immune system attacks and destroys the insulin-producing cells (beta cells) in the pancreas, leading to increased blood sugar levels and potential multiple organ complications later in life (cardiovascular disease, nerve damage, kidney damage, eye damage, foot damage, skin conditions, hearing impairment). Therapies focused on preserving functional beta cells, gaining immune tolerance, and inducing beta cell regeneration are a priority for the treatment of the disease. Preliminary studies from our lab suggest that the polysaccharide Dextran Sulfate (DS) is a prosurvival agent for the pancreatic beta cell, increases markers of immune tolerance, prevents the development of T1D in pre-diabetic mice, and more importantly, reverses diabetes in ~70% of diabetic mice. Collectively, published studies and our preliminary data suggest a promising therapeutic effect of DS for T1D. Our hypothesis is that DS reverses T1D by favoring the survival and maintaining the function of the beta cell and by modulating the immune system to enhance tolerance. To determine whether our hypothesis is correct, we will (1) determine the effect and molecular mechanisms mediated by DS on beta cell survival and function in the context of T1D; (2) analyze the efficacy of DS treatment alone or in combination with a regenerative agent such as hepatocyte growth factor for reversing diabetes in NOD mice; and (3) analyze the effect of DS in human immune cells as a previous step to the initiation of clinical trials in subjects with T1D. The proposed studies will provide significant information regarding the therapeutic potential of DS for T1D and the mechanisms involved in these beneficial effects.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710364
Entities
People
- Dirk Homann
Organizations
- Icahn School of Medicine at Mount Sinai
- United States Army