Authors:
Nathan R. Selden, MD, PhD, Daniel J. Guillaume, MD, Stephen L. Huhn, MD, Thomas K. Koch, MD, Amira Al-Uzri, MD, & Robert D. Steiner, MD
Summary:
Introduction - An open-label dose-escalation Phase I trial of a highly purified, expandable population of human central nervous system stem cells (HuCNS-SC) was conducted in subjects with advanced stage infantile and late-infantile neuronal ceroid lipofuscinoses (INCL and LINCL). This investigation is the first US FDA authorized use of human neural stem cells for clinical testing.
Methods - Six pediatric subjects underwent bilateral intracerebral and intraventricular transplantation of HuCNS-SC. The low-dose cohort received a target dose of 500 million cells, and high-dose cohort received a target dose of 1 billion cells, followed by 12 months of immunosuppression. Subjects were assessed both pre- and post-transplant with a comprehensive battery of tests and brain magnetic resonance (MR) imaging.
Results - HuCNS-SC transplantation in combination with immunosuppression was well-tolerated by all six subjects. The subjects neurological and neuropsychological outcomes were consistent with the underlying disease. One subject with INCL expired due to natural progression of the disease 11 months post-transplant. A brain autopsy revealed no HuCNS-SC related toxicity. DNA PCR testing of post-mortem brain tissue provided evidence of donor cell engraftment and survival. The remaining five subjects completed the Phase I trial assessments and enrolled in a separate 4-year long-term follow-up study.
Conclusions - This Phase I study, representing the first clinical trial of purified and expanded neural stem cells, utilized a novel dosing and implantation paradigm. Based on the safety profile and post-mortem evidence of donor cell survival, further investigation of HuCNS-SC transplantation appears warranted.
Source:
2010 American Association of Neurological Surgeons Annual Meeting; Pennsylvania Convention Center, Philadelphia, PA, 64759 (05/03/10)