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A proposed combinatorial treatment for type 1 diabetes

by Matthew Greseth

Type 1 diabetes (T1D) is a chronic condition in which the body’s own immune system attacks and destroys beta cells in the pancreas. Once the beta cells are destroyed, the pancreas can no longer produce insulin. Currently, there is no cure for T1D and treatment focuses on managing blood sugar levels. Researchers at MUSC, including Hongjun Wang, Ph.D., professor in the Department of Surgery in the College of Medicine, and co-investigator Charlton B. Strange, M.D., professor in the College of Medicine, hope to offer patients a better alternative. Wang received a grant of more than $2 million from the National Institutes of Health to explore novel treatments for T1D patients.

New strategies for T1D intervention should effectively target the immune system and protect/regenerate beta cells. To date, there is no single intervention that targets these areas, and novel combined therapies would be beneficial for such a complex disease.

The use of mesenchymal stem cells (MSCs) as a therapeutic tool represents a promising new intervention. Evidence suggests that MSC therapy can effectively target several injury pathways in a variety of autoimmune and inflammatory diseases, something that most pharmacological interventions cannot accomplish. In fact, recent studies from the Wang lab have shown that infusion of MSCs promotes T regulatory cell generation, a subpopulation of T cells that modulate the immune response, and prevents beta cell death. However, most human studies using MSCs alone have not been successful at sustained suppression of the autoimmune response.

The newly funded work is going further by combining MSCs with the protective effects of alpha 1-antitrypsin (AAT). AAT protects tissues from the damaging effects of inflammation by decreasing insulin autoantibodies and promoting T regulatory cell function. Using a humanized mouse model of T1D, the group will combine Wang’s expertise in islet transplantation and immunology with Strange’s expertise in AAT biology and genomics to monitor the sustained efficacy of this combined therapy on the immune system and the preservation/reconstitution of beta cells.