Gene and cell delivery to the degenerated striatum: status of preclinical efforts in primate models

Abstract

Significant progress has been achieved in developing restorative neurosurgical strategies for movement disorders on the basis of preclinical gene and cell therapy experiments in primates. Because of the unique similarities between human and primate anatomy and physiology, experiments in primate models are the critical step in translating these innovative neurosurgical treatment concepts into successful human applications. To clarify progress toward this goal, we have examined recent preclinical data regarding the delivery of gene and cell therapy to the lesioned primate striatum. Improved behavioral outcomes after in vivo gene transduction, achieved by brain delivery of adeno-associated vectors, have resulted in the initiation of ongoing clinical trials. Cell transplantation experiments are transitioning from the grafting of fetal tissue, which has met with mixed clinical success, to the grafting of expanded neural stem cells, for which preliminary results in primates are encouraging. Careful attention to the surgical delivery parameters for these agents in primate studies, along with the ability to realistically model imaging and behavioral outcomes in these animals, is essential for optimizing the restoration of function for patients. The authors review data obtained from primate models that form the basis for ongoing clinical trials to consider how new preclinical models should be developed to answer questions that arise from experimental clinical data.