Dr. DeLuca's team will build on its earlier research on mutant forms of the virus to explore how therapeutic proteins made by HSV-transferred genes can alter the function of islet genes and affect islet survival. University of Pittsburgh School of Medicine Dr. Robbins' project will develop and test new vectors, both in islets in vitro and in animals following islet transplantation. The goal is to find the right vectors for human gene therapy clinical trials for diabetes. Diabetic neuropathy can have many dangerous effects. Because it is difficult for some people with diabetes to feel pain in their limbs, they may ignore scratches or wounds that can become infected and eventually gangrenous.
Nerve damage causes other people with diabetes constant pain in their limbs.
Finally, damage to the nerves that control internal organs, such as the heart, can lead to life-threatening conditions including heart failure. The project under the direction of Dr. Fink and Dr. Glorioso will attempt to prevent the progression of diabetic neuropathy by using a vector based on the herpes simplex type 1 virus to infect neurons with genes that produce small protein molecules called growth factors. The project will build on the investigators' previous research on animals, which indicates that treating animals with a vector that expresses nerve growth factor may prevent nerve damage in other models of neuropathy. This core will construct and provide viral vectors for each of the projects. The overall goal of the core is to develop and provide the most appropriate vectors for each project for long-term or regulated gene expression that could be used for clinical applications.