Research Project
6337127
Sertoli cells are post-mitotic cells originating in the testes. They express and secrete many trophic, nutritive and regulatory proteins that are able to provide trophic and immunologic support for the developing germ cell. These characteristics make them an ideal cell candidate for an adjunct to traditional neural transplantation for neurodegenerative diseases such as Parkinson's disease. This is a novel therapeutic approach that through trophic and immune support could increase the survival of transplanted neurons and decrease the need for long-term treatment with immunosuppressants. This Phase I research program proposes to determine the source of the most efficacious cells using in vitro screening assays, determine the Sertoli to neuron ratio that produces optimal neuronal survival through completion of a thorough in vivo dose-response relationship, and determine whether these cells continue to provide immune protection when grafted across species. The success of these studies in an animal model of Parkinson's disease has important implications for the therapeutic potential of these cells as graft facilitators or as the vehicle for long-term local delivery of a trophic cocktail in other neurodegenerative diseases. PROPOSED COMMERCIAL APPLICATIONS: Neural transplantation has the potential to reverse progressive degeneration in diseases such as PD, Motor Neuron Disease, Stroke. However, neuronal survival is poor and a host-generated immune response to the transplanted cells may further destroy the graft. Sertoli cells provide a novel, naturally-occurring technology to enhance neuronal survival, provide localized immunosuppression without the health risks of long-term systemic suppression and possibly decrease disease symptoms beyond currently attainable levels.
