Can gene therapy make pancreas and islet transplantation obsolete?

Abstract

Purpose of review The current research on alternative treatment options for type 1 diabetes mellitus (T1DM) with special emphasis on gene therapy is discussed. The potential clinical applicability of new approaches is reviewed in the context of contemporary therapies. Recent findings Among a variety of target cells available for insulin gene therapy, preferred cells are hepatocytes for a regulated and myocytes for a basal nonregulated insulin gene expression. An ideal method of gene delivery has not emerged but a few promising methods merit further investigations. For example, new helper-dependent adenoviral systems may provide sustained gene expression. Introduction of β-cell-specific transcription factors in non-β cells can generate insulin secreting cells that possess a complete regulated secretory machinery. Summary Insulin gene therapy appears to be the most feasible approach among novel alternatives to treat T1DM. The major obstacle remains a safe and effective gene delivery method for long-term insulin expression yielding a clearly superior quality of life. An episomal insulin expression, glucose-regulated only at the level of transcription, with an inherent delay in release-response is not comparable with native β-cell function but it represents a useful compromise until an ideal solution is found. Although still in its early phase, attempts to generate insulin-secreting cells from autologous cells by transdifferentiation involving soluble factors and transgene expression seem promising, with potential of approaching near ideal glycemic control.