Preventing type 1 diabetes mellitus: The promise of gene therapy

Type 1 (insulin-dependent) diabetes mellitus is an autoimmune disease that has no cure. Closed-loop insulin administration strategies and approaches for replacement of the insulin-producing β cells may offer improved treatments, which could delay or prevent diabetes complications. In the long run, however, prevention of type 1 diabetes in susceptible individuals represents the best chance for reducing the toll of the disease. Prevention of type 1 diabetes will require reliable methods for early diagnosis of predisposition to the disease, using improved genetic and serological screening on a wide scale. Identification of the primary antigenic target(s) for autoimmunity will allow intervention in prediabetes stages aimed at the induction of antigen-specific tolerance. In addition to manipulation of the immune system, the susceptibility of β cells to autoimmunity could be reduced. A number of genes have been shown to increase β-cell resistance to immune effector molecules in animal models and cultured β-cell lines. These genes could be used for preventive gene therapy of type 1 diabetes mellitus if expressed in β cells prior to the onset of autoimmune destruction. This prospect depends on the development of safe and efficient vectors, and approaches for cell-specific targeting of these vectors to β cells in vivo.