Human Neural Stem Cell-Based Cell- and Gene-Therapy for Neurological Diseases

Abstract

Cell replacement therapy and gene transfer to the diseased or injured brain have provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases. However, the paucity of suitable cell types for cell replacement therapy in patients suffering from neurological disorders has hampered the development of this promising therapeutic approach. In recent years, neurons and glia have successfully been generated from stem cells such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and neural stem cells (NSCs), and extensive efforts by investigators to develop stem cell-based brain transplantation therapies have been carried out. We have previously generated continuously dividing immortalized cell lines of NSCs by introduction of oncogenes and used these immortalized NSC lines in cell and gene therapy studies in animal models of Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), stroke, and brain tumors. Recently the FDA approved the City of Hope Medical Center in California to proceed with the first human NSC clinical trial to treat brain tumor and seven patients are receiving this suicide gene therapy. This human NSC line was produced in my laboratory in UBC and the study is the first to use human NSC line to deliver an anticancer therapeutic agent.