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Original research
Phase 1 study of safety and preliminary efficacy of intranasal transplantation of human neural stem cells (ANGE-S003) in Parkinson’s disease
  1. Shenzhong Jiang1,
  2. Han Wang2,
  3. Chengxian Yang1,
  4. Feng Feng3,
  5. Dan Xu2,
  6. Mengyu Zhang2,
  7. Manqing Xie2,
  8. Ruixue Cui4,
  9. Zhaohui Zhu4,
  10. Chenhao Jia4,
  11. Linwen Liu5,
  12. Lin Wang2,
  13. Xunzhe Yang2,
  14. Yingmai Yang2,
  15. Honglin Hao2,
  16. Zhaoxi Liu3,
  17. Zhihong Wu6,
  18. Ling Leng6,
  19. Xiaoxin Li6,
  20. Xicai Sun7,
  21. Xiongfei Zhao7,
  22. Jinfang Xu8,
  23. Yi Zhang1,
  24. Xinhua Wan2,
  25. Xinjie Bao1,9,
  26. Renzhi Wang1,10
  1. 1 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
  2. 2 Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
  3. 3 Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  4. 4 Department of Nuclear Medicine, Peking Union Medical College Hospital and Chinese Academy of Medical Science, Beijing, China
  5. 5 Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  6. 6 Stem Cell and Regenerative Medicine Lab, Medical Research Center, Translational Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  7. 7 Shanghai Angecon Biotechnology Co Ltd, Shanghai, Shanghai, China
  8. 8 Department of Health Statistics, Second Military Medical University, Shanghai, China
  9. 9 State Key Laboratory of Common Mechanism Research for Major Diseases, Beijing, China
  10. 10 School of Medicine, Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, China
  1. Correspondence to Dr Xinjie Bao; baoxinjie1{at}pumch.cn; Dr Renzhi Wang; wangrz{at}126.com; Dr Xinhua Wan; xhwanpumch{at}hotmail.com

Abstract

Background Intranasal 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.

Methods This 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.

Results 7 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.

Conclusions Treatment 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.

  • PARKINSON'S DISEASE

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Footnotes

  • X @ffever844

  • SJ, HW and CY contributed equally.

  • Contributors SJ, HW and CY wrote the original draft and revised later versions with key revisions from all authors. HW and XW recruited patients. DX, LW, XY, MX and HH screened patients and collected data. CY coordinated patients’ visits. DX, MX and MZ performed all the scales. FF and ZL performed the MRI scanning. RC, ZZ, CJ and LL performed the PET scanning and analysed the imaging. XS and XZ developed the NSC product. LL, XL and ZW implemented the quality control of NSCs. JX and SJ performed data analysis and interpretation. YZ provided nursing care to patients in wards. XB did all the surgeries. XW, XB and RW designed and supervised the study. All authors reviewed and approved the final report. XB acts as the guarantor of the manuscript.

  • Funding This study was funded by Angecon Biotechnology Co, Ltd (Grant number: N/A)

  • Competing interests XS and XZ are employees of Angecon Biotechnology Co, Ltd. The other authors declare no competing interests.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.