Introduction: An open-label dose-escalation Phase I trial of a highly purified, expandable population of human central nervous system stem cells (HuCNS-SC, StemCells, Inc., Newark, CA) was conducted in subjects with advanced stage infantile and late-infantile neuronal ceroid lipofuscinoses (NCL). This investigation was the first U.S. FDA authorized use of human neural stem cells for clinical testing. The current report summarizes the outcome of the separate 4 year long-term follow-up (LTFU) study which was conducted for post-transplantation surveillance.
Methods: Six subjects underwent bilateral intracerebral and intraventricular transplantation of HuCNS-SC as part of the Phase I study and surviving subjects enrolled in the LTFU for 4 years of observation. Subjects were routinely assessed with a comprehensive battery of tests and brain MR imaging.
Results: HuCNS-SC transplantation in combination with immunosuppression was well tolerated by all subjects. Neurological and neuropsychological outcomes were consistent with NCL progression during the Phase I study. One subject expired during the Phase I study at 11 months post-transplant and two subjects expired during the LTFU study at 30 and 41 months post-transplant, respectively. DNA PCR testing of post-mortem brain tissue from two of these subjects provided evidence of donor cell engraftment. There were no safety concerns attributed to the cell transplant during the conduct of the LTFU study, and analysis of the preliminary efficacy data will be presented.
Conclusions: This Phase I and LTFU study represent the first-in-human clinical use of purified neural stem cells. The completion of the subsequent LTFU study provides the longest and most comprehensive follow-up data set involving neural stem cell transplantation in human subjects.
Patient Care: This phase I trial of human neural stem cell transplantation will help advance the potential of neuronal stem cell therapy for neurodegenerative disorders.
Learning Objectives: Participants will be able to identify the rationale for and potential benefits of neuronal stem cell transplantation for neurodegenerative disorders, as well as describe the results of the first in-human trial.