Therapeutic strategies for Type 1 and Type 2 diabetes mellitus.
Although diabetes mellitus is a manageable disorder, the associated complications that result in significant morbidity and mortality worldwide necessitate novel approaches of pharmacologic, cell, and gene therapy for an eventual cure. A significant number of animal studies have demonstrated the potential of restoring normoglycemia by islet transplantation in the context of immunoregulation achieved by gene transfer of immunoregulatory genes to allo- and xenogeneic islets ex vivo. Examples include viral vector-mediated gene transfer of immunosuppressive cytokines, proteins that block co-stimulation and molecules that prevent apoptotic cell death. Additionally, gene and cell therapy has also been used to induce tolerance to auto- and alloantigens and to generate the tolerant state in autoimmune rodent animal models of Type 1 diabetes mellitus (T1DM) or rodent recipients of allogeneic/xenogeneic islet transplants. Gene transfer of putative autoantigens is one example. The achievements of gene and cell therapy in Type 2 diabetes mellitus (T2DM) are less evident, but seminal studies promise that this modality can be relevant to treat and perhaps prevent the underlying causes of the disease including obesity and insulin resistance. Herein, we present an overview of the current status of drug, gene and cell therapy for T1DM and T2DM and we propose novel therapeutic options that could be clinically useful.
Giannoukakis
N
N
Dept of Pathology, and Diabetes Institute, University of Pittsburgh School of Medicine, Rangos Research Center, PA 15213, USA. ngiann1@pitt.edu
Pietropaolo
M
M
Trucco
M
M
D000818:Animals; D017209:Apoptosis; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000517:prevention & control / Q000628:therapy*; D015316:Genetic Therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007108:Immune Tolerance / Q000235:genetics; D007333:Insulin Resistance; D016381:Islets of Langerhans Transplantation; D009765:Obesity / Q000517:prevention & control; D014162:Transfection
D001324:Autoantigens; D016207:Cytokines; D007004:Hypoglycemic Agents