Jin Woo Chang, Han Kyu Na, Kyung Won Chang, Chan Wook Park, Dohun Kim, Do-Hun Kim, Chul‐Yong Park, Chul-Yong Park, Jang Hyeon Eom, Seung Taek Nam, Ki-Sang Jo, Mi-Young Jo, Sung Kyoung Choi, Hye‐Jin Hur, Minseok Kim, Minseok Kim, Dae-Sung Kim, Myoung Soo Kim, Dong‐Youn Hwang, Myoung Soo Kim, Inkyung Jung, Jongwan Kim, Myung Soo Cho, Phil Hyu Lee, Dong Wook Kim, Dong Wook Kim
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.