Gene therapy in diabetes mellitus: promises and piffalls

After some initial disappointments, the field of gene therapy is now gaining confidence and momentum. Recent improvements in gene transfer techniques promise targeted and supra-threshold levels of transgene expression leading to the desired therapeutic effects. This increase in optimism has spread to thefield of diabetes research. Firstly, the recent developments in gene transfer techniques are now being tested on the pancreatic insulin producing beta-cell. For many gene therapy strategies in the treatment of diabetes, transfection of insulin producing cells is a prerequisite. Secondly, if efficient and safe vectors that transduce beta-cells in vivo or ex vivo are made available, autoimmune beta-cell destruction in type 1 diabetes could be prevented. In this strategy, it is envisaged that gene therapy will protect the remaining beta-cell mass in newly diagnosed diabetics or pre-diabetic individuals at a high risk of becoming diabetic from autoimmune destruction. Thirdly, attempts are being made to genetically engineer cells to become artificial beta-cells. Such cells could conceivably compensate for the lost endogeneous alpha-cell mass and restore a regulated insulin secretion. This review will attempt to predict the future of gene therapy in the treatment of diabetes.