Neural Stem Cell Based Therapy For Parkinson’s Disease (S48.007)

OBJECTIVE: To study therapeutic potential of human parthenogenetic stem cell derived neural stem cells in various animal models of Parkinson’s disease. BACKGROUND: We have previously demonstrated that hpNSCs slow down the progression of Parkinson’s disease (PD) and significantly increase brain dopamine levels in pre-clinical animal models. Here we present the results of four IND-enabling studies testing the pharmacology, toxicology, biodistribution, and efficacy of hpNSCs in rodents and non-human primates. DESIGN/METHODS: hpNSCs were manufactured under cGMP conditions and tested in four animal studies: 1- an efficacy study in 6-OHDA-lesioned rats with PD symptoms, 2- an acute toxicity study in immunodeficient rats, 3- a large-scale pharmacology, toxicology, tumorigenicity study with biodistribution assessment in immunodeficient rats, and 4- pharmacology and toxicology study with biodistribution assessment in MPTP-lesioned African green monkeys with moderate to severe parkinsonism. A battery of assays including clinical observation, behavioral testing, hematology, clinical chemistries, necropsy, histopathology, biodistribution by qPCR, immunohistochemistry, and dopamine analysis by HPLC were performed to determine the safety and efficacy profile of the cells. RESULTS: Results of these animal studies demonstrate that transplantation of hpNSCs is safe and well tolerated. hpNSCs do not induce dyskinesia, systemic toxicity, or host immune rejection. Analysis of tissues showed no signs ectopic tissue, tumors, hyperproliferation, or biodistribution of cells to non-target organs. hpNSCs survived long-term in the brain of transplanted animals, increased dopamine levels and improved motor funtion. hpNSCs migrated to injury areas in the substantia nigra, provided neuroprotection and neurotrophic support, and differentiated into dopaminergic neurons and other neural cell types. CONCLUSIONS: These results confirm that human parthenogenetic stem cell derived neural stem cells are safe and effective treatment of Parkinson’s disease. Study Supported by: International Stem Cell Corp Disclosure: Dr. Semechkin has received personal compensation for activities with International Stem Cell Corporation as an employee. Dr. Gonzalez has received personal compensation for activities with International Stem Cell Corp. as an employee. Dr. Garitaonandia has received personal compensation for activities with International Stem Cell Corporation as an employee. Ms. Abramihina has received personal compensation for activities with International Stem Cell Corporation as an employee. Dr. Poustovoitov has received personal compensation for activities with the International Stem Cell Organization as an employee. Dr. Crain has nothing to disclose. Dr. Noskov has received personal compensation for activities with International Stem Cell Corporation as an employee. Dr. Laurent has nothing to disclose. Dr. Snyder has nothing to disclose. Dr. Redmond has nothing to disclose.