Phase 1/2a clinical trial of hESC-derived dopamine progenitors in Parkinson’s disease
Parkinson's disease (PD) has long been considered an appropriate candidate for cell replacement therapy. We generated high-purity dopaminergic progenitors (A9-DPCs) from human embryonic stem cells and evaluated their safety and exploratory efficacy in a single-center, open-label, dose-escalation phase 1/2a trial (NCT05887466) for PD patients. Twelve patients with moderate-to-severe PD received bilateral putamen transplantation of low-dose (3.15 million cells; n = 6) or high-dose (6.30 million cells; n = 6) A9-DPC with immunosuppression. No dose-limiting toxicities or graft-related adverse events were observed. At 12 months, off-medication Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III scores and Hoehn and Yahr stage improved, with greater motor improvements in the high-dose group. Dopamine transporter positron emission tomography (PET) imaging showed increased posterior putamen uptake with greater uptake in the high-dose group after transplantation, supporting graft survival. These findings indicate that bilateral transplantation of A9-DPC is safe and may improve parkinsonian motor symptoms in patients with PD.
Authors
- Han Kyu Na (ORCID: https://orcid.org/0000-0002-2093-1641)
- Kyung Won Chang (ORCID: https://orcid.org/0000-0002-8697-1195)
- Phil Hyu Lee (ORCID: https://orcid.org/0000-0001-9931-8462)
- Hye‐Jin Hur
- Chul‐Yong Park (ORCID: https://orcid.org/0000-0002-4467-9268)
- Jin Woo Chang (ORCID: https://orcid.org/0000-0002-2717-0101)
- Myung Soo Cho (ORCID: https://orcid.org/0000-0002-2679-3251)
- Seung Taek Nam
- Inkyung Jung (ORCID: https://orcid.org/0000-0002-5885-2754)
- Sang Hyun Park (ORCID: https://orcid.org/0000-0003-0612-2562)
- Jongwan Kim (ORCID: https://orcid.org/0000-0003-2623-7105)
- Dohun Kim (ORCID: https://orcid.org/0000-0001-8304-0232)
- Myoung Soo Kim (ORCID: https://orcid.org/0000-0002-1773-1374)
- Minseok Kim (ORCID: https://orcid.org/0000-0002-3651-536X)
- Dae‐Sung Kim (ORCID: https://orcid.org/0000-0001-6690-5943)
- Sung Kyoung Choi
- Chan Wook Park
- Dong‐Youn Hwang (ORCID: https://orcid.org/0000-0002-2332-9461)
- Mi-Young Jo
- Jang Hyeon Eom
- Sarang Kim
- Ki-Sang Jo
- Dong Wook Kim (ORCID: https://orcid.org/0000-0001-6106-9894)
Institutions
- Yonsei University (KR)
- Korea University (KR)
- Samsung Medical Center (KR)
- Bio-Medical Science (South Korea) (KR)
- CHA University (KR)
- Korea University (JP)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Cell
- Published
- 2025-10-13
- DOI
- https://doi.org/10.1016/j.cell.2025.09.010
- Citations
- 8
- Primary Topic
- Neurological disorders and treatments
- Type
- article
- Field-Weighted Citation Impact
- 11.11