The ever increasing population and life expectancy of the human race translates into an emerging need for safe and effective strategies for neurodegenerative disease therapy. This proposed study aims to improve previous research conducted on neural stem cell (NSC) based neurodegenerative disease therapies by altering gene expression in these cells via lentiviral vectors prior to implantation. Specifically, the CXCR4 and/or ER/GR genes will be overexpressed in NSCs for the purpose of improved homing sensitivity to the damaged CNS regions and ameliorating the deleterious effect of elevated steroid hormone levels present in neurodegenerative conditions, respectively. Additionally, co-administration of erythropoietin will be explored for potential improvement of NSC based therapy through its anti-inflammatory properties and enhancement of lesion repair from increased recruitment and proliferation of native and implanted NSCs. Initially, a neurodegenerative condition will be simulated through kainic acid induced hippocampal lesioning in a murine biological system. Next, the normal and CXCR4 modified NSCs will be infused into the animal model via intravenous and direct intracranial injection into the brain. Depending on the NSC delivery efficiency observed in this preliminary trial, subsequent experiments testing all the proposed improvements will involve either the minimally invasive intravenous administration or direct intracranial injection. Finally, assessment of therapeutic outcome will involve tracking the migration of the implanted NSCs, histology of lesion site, immunohistochemistry and in vivo functional recovery testing.