Research Group

  • Dr. Tausif Alam, Principal Investigator
  • Dr. Michael J. MacDonald, Collaborator
  • Dr. James S. Malter, Collaborator


  • University of Wisconsin, Madison, USA


  • Gene Therapy-Based Treatment for Insulin-Dependent Diabetes Mellitus

Insulin-dependent diabetes mellitus (IDDM) is caused by selective autoimmune destruction of insulin-producing β-cells of endocrine pancreas. Two therapies are currently available for IDDM, and both have serious limitations. The first therapy, based on daily insulin injections, inadequately controls hyperglycemia and consequently does not prevent the long-term damage associated with the disease. The second therapy, transplantation of whole pancreas or of pancreatic islets, precisely regulates blood sugar levels, but too few donor organs of suitable quality are available. Recent advances in cellular/molecular engineering now allow attempts for an alternative therapy by replacing the function of β-cell by a non-β-cell, engineered to provide insulin only when needed. For a precise gluco-homeostasis, β-cells instantaneously release stored insulin in response to high glucose levels. Therefore, the majority of studies attempting to generate a surrogate β-cell have focused on modifying cells that possess regulated secretory mechanism, but they have been unsatisfactory.

Our novel approach is based on recipient’s own liver cells, engineered for glucose-regulated de novo synthesis and secretion of insulin, eliminating the need to duplicate a complex and incompletely understood mechanism of regulated insulin secretion of β-cells. The preliminary studies performed in cell culture and in diabetic rats provide ample proof of principle. The proposed optimizations will further improve the efficacy of transduced liver cells to normalize glucose levels of diabetic experimental rats. Using our approach, the diabetic recipients of insulin-gene-engineered hepatocytes may experience a transient, mild hyperglycemia in the minutes after eating, but should be able to avoid the chronic hyperglycemia that typically occurs with insulin injections alone, avoiding severe diabetes-associated complications. Success in our approach will provide a basis for the future gene therapy-based IDDM treatment that could be administered before the development of serious hyperglycemia-related complications. Furthermore, the use of autologous liver cells may eliminate the necessity of immunosuppression.