PT  - JOURNAL ARTICLE
AU  - Russell Kern
AU  - Ibon Garitaonandia
AU  - Rodolfo Gonzalez
AU  - Glenn Sherman
AU  - Andrey Semechkin
AU  - Evan Snyder
AU  - Azmin Shahrul
AU  - Girish Nair
AU  - Andrew Evans
TI  - PRELIMINARY RESULTS OF THE PHASE I CLINICAL STUDY EVALUATING NEURAL STEM CELL BASED THERAPY FOR PARKINSON’S DISEASE (S4.004)
DP  - 2017 Apr 18
TA  - Neurology
PG  - S4.004
VI  - 88
IP  - 16 Supplement
4099  - http://n.neurology.org/content/88/16_Supplement/S4.004.short
4100  - http://n.neurology.org/content/88/16_Supplement/S4.004.full
SO  - Neurology2017 Apr 18; 88
AB  - Objective: Evaluate the safety and functional activity of human pluripotent stem cell derived neural stem cells (ISC-hpNSC) transplanted into the striatum and substantia nigra of patients with Parkinson’s disease (PD).Background: Extensive preclinical studies have demonstrated that intranigrostriatal transplantation of cGMP manufactured ISC-hpNSC is safe, well tolerated at high doses and does not induce systemic toxicity or tumors. ISC-hpNSC provides neurotrophic support, immunomodulation and cell replacement which lead to increased dopamine levels and improvement in neurological scores in preclinical PD models. Based on these results, the Australian TGA granted approval to conduct a First-In-Human study to evaluate the safety and functional activity of ISC-hpNSC in PD patients (ClinicalTrials.gov: NCT02452723), making it the world’s first pluripotent stem cell based therapy for PD.Design/Methods: In this single arm, open label, dose escalating Phase I study, 12 patients, divided into 3 cohorts of 4, are injected with 30, 50 or 70 million ISC-hpNSC. Patients receive stereotactic bilateral injections of 7 cell deposits per hemisphere into the caudate nucleus, putamen and substantia nigra. Patients are evaluated for 12 months with a 5 year long-term follow-up. The primary endpoint is to assess the incidence of treatment-emergent adverse events. Secondary endpoints evaluate clinical improvement compared to baseline using UPDRS, PDQ-39, BDI, CGI, QUIP-RS, AIMS, MOCA, 18F-dopa PET and MRI.Results: The first patient of the first cohort was successfully transplanted with 30 million ISC-hpNSC. Delivery of the cells went according to plan without any complications or safety issues associated with the administration procedure or immunosuppressive regimen. Interim safety and efficacy data of the rest of the patients of the first cohort receiving 30 million ISC-hpNSC will be presented.Conclusions: This First-In-Human study suggests that transplantation of ISC-hpNSC is safe and has the potential to slow down disease progression.Disclosure: Dr. Kern has received personal compensation as an employee of International Stem Cell Corporation. Dr. Garitaonandia has received personal compensation for activities with International Stem Cell Corporation as an employee. Dr. Gonzalez has received personal compensation for activities with the Iternational Stem Cell Corporation as an employee. Dr. Sherman has received personal compensation for activities with International Stem Cell Corporation as an employee. Dr. Semechkin received compensation for activities with International Stem Cell Corporation as an employee. Dr. Snyder has nothing to disclose. Dr. Shahrul has received personal compensation for activities with International Stem Cell Corporation. Dr. Nair has received personal compensation for activities with International Stem Cell Corporation. Dr. Evans has received personal compensation for activities with Boehringer Ingelheim and Novartis as an advisory board member and from International Stem Cell Corporation.