• Shenzhong Jiang, Han Wang, Chengxian Yang, Feng Feng, Dan Xu, Mengyu Zhang, Manqing Xie, Ruixue Cui, Zhaohui Zhu, Chenhao Jia, Linwen Liu, Lin Wang, Xunzhe Yang, Yingmai Yang, Honglin Hao, Zhaoxi Liu, Zhihong Wu, Ling Leng, Xiaoxin Li, Xicai Sun, Xiongfei Zhao, Jinfang Xu, Yi Zhang, Xinhua Wan, Xinjie Bao, and Renzhi Wang.
• Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
• J. Neurol. Neurosurg. Psychiatr. 2024 Nov 18; 95 (12): 110211111102-1111.

BackgroundIntranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial.MethodsThis was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy.Results7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels.ConclusionsTreatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

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