Development of a Cell Replacement Therapy Product for Insulin Dependent Diabetes

With a current prevalence of greater than 170 million individuals world-wide, diabetes has attained epidemic proportions. The widespread secondary complications this disease extract a relentless and costly toll on the patients and health care establishment required for their treatment. To date, cellular replacement therapies for the treatment of diabetes has been performed either by transplantation of whole pancreas, or via infusion of isolated primary pancreatic islets into the portal vein . While effective, the availability of such procedures is severely limited for the treatment of the general diabetes population since it relies upon the extremely limited supply of organs from deceased donors.

One approach to overcoming the problem of insufficient organ and islet supply is to generate glucose responsive human insulin secreting pancreatic islet cells from stem cell populations. Only human embryonic stem cells (hES cells) demonstrate sufficient cell expansion capacity to achieve production levels needed to treat patients with diabetes. Furthermore, hES cells are capable of efficiently and rapidly progressing through a series of defined steps to generate most cell types found in the human body, but more importantly, pancreatic beta cells that release insulin in response to changing blood glucose levels. In a recent breakthrough, stem cell derived beta cells have been produced for the first time, providing confirmation that hES cells can serve as a realistic and renewable source of functional glucose responsive islet cells.

To achieve the goal of producing a safe product for clinical trials in patients with diabetes, the disease team must meet the following objectives: 1.) Identification and characterization of the clinical cell product; 2.) Development of methods to sufficiently purify the clinical cell product; 3.) Development of scale-up methodologies sufficient for achieving clinical trial product supplies; 4.) Design and completion of safety studies; 5.) Identification of implantation site for human clinical trials; 6.) Design of clinical trial; 7.) Development of product shipping and storage procedures; 8.) Development of FDA approved manufacturing process; 9.) FDA approved product facility construction and validation; 10) Submission of product and process documentation to the FDA sufficient to begin human clinical trials.

The disease team members critical to efficiently realizing these objectives include a consortium of scientists and managers who are currently fully focused on the realization of these goals. The team includes experienced stem cell researchers who have already developed glucose sensing pancreatic islet cells from hES cells. Together with these hES cell experts the team will include experts in the development, scale-up, manufacture and commercialization of cell-based therapies and on the safety and toxicology studies required for clinical trials with human cell therapy products.