Protecting Pancreatic Islet Grafts from Rejection

DESCRIPTION (provided by applicant): Type 1 diabetes mellitus (DM) is an autoimmune disease that destroys insulin-producing cells of the pancreas. Type 1 DM affects an estimated one million Americans and usually finds its onset in the young. It is one of the leading causes of kidney disease, peripheral neurological diseases and also blindness. It shortens the lifespan primarily through premature cardiovascular mortality. It results in significant health care expenditures for patients, their families and society as a whole. Although blood glucose levels can be well controlled by insulin substitution therapy, some of the DM complications cannot. Therefore, reconstitution of normal pancreatic islet function has been an important DM treatment goal. This has included the transplantation of allogeneic pancreatic islets. Immune suppression protocols have been developed that allowed the successful transplantation of islets. Unfortunately, they are fraught with significant immediate and chronic side effects that make their use especially problematic for children. Presently, only patients suffering from unstable forms of DM are considered transplantation candidates. Isogenis' mission has been the development of innovative immune inhibitory agents that employ highly specific, yet effective immune suppression approaches. Isogenis based its technology on the natural veto immune inhibitory phenomenon. Isogenis uses viral vectors that transfer the CD8 a-chain and thus specific immune suppression to transplants. Isogenis already reached the crucial developmental milestone of proof-of-functional utility of its veto vector approach. Isogenis established that simple extracorporal veto vector transductions permanent protected pancreatic islets from rejection by fully allogeneic recipient animals. Isogenis now proposes to use a nonhuman primate model to test the functionality, pharmacology and toxicity of the clinical version of a veto vector and thus to complete the pre-clinical trial stage of veto vectors in pancreatic islet transplantation. In parallel, Isogenis will optimize protocols of veto vector production and purification and veto vector-based immune suppression regimens. These studies will allow Isogenis to collect data for the filing of an 'investigational new drug' (IND) with the 'Food and Drug Administration'. Type 1 diabetes mellitus (DM) is an autoimmune disease that destroys insulin-producing cells of the pancreas. Type 1 DM affects an estimated one million Americans and is one of the leading causes of kidney disease, peripheral neurological diseases and also blindness. Transplantation of pancreatic islets can provide a permanent cure. However, present immune suppression regimens used for organ transplantation are fraught with significant immediate and chronic side effects that make their use especially problematic for children. Isogenis is developing novel immune suppressive compounds that are less toxic,a are used short-term; yet prevent the rejection of transplanted tissue with similar if not improved efficacy.