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. 2024 Jan 4;31(1):25-38.e8.
doi: 10.1016/j.stem.2023.11.009. Epub 2023 Dec 11.

Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease

Sanghyun Park  1 , Chan Wook Park  1 , Jang Hyeon Eom  2 , Mi-Young Jo  2 , Hye-Jin Hur  3 , Sung Kyoung Choi  2 , Jae Souk Lee  1 , Seung Taek Nam  2 , Ki-Sang Jo  2 , Young Woo Oh  4 , Jungil Lee  4 , Sieun Kim  4 , Do-Hun Kim  3 , Chul-Yong Park  3 , Su Jin Kim  5 , Ho-Young Lee  5 , Myung Soo Cho  2 , Dae-Sung Kim  6 , Dong-Wook Kim  7
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Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease

Sanghyun Park et al. Cell Stem Cell. .
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Abstract

Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities. Various doses of mDA progenitors were transplanted into hemi-parkinsonian rats, and a significant dose-dependent behavioral improvement was observed with a minimal effective dose range of 5,000-10,000 mDA progenitor cells. These results provided insights into determining a low cell dosage (3.15 million cells) for human clinical trials. Based on these results, approval for a phase 1/2a clinical trial for PD cell therapy was obtained from the Ministry of Food and Drug Safety in Korea, and a clinical trial for treating patients with PD has commenced.

Keywords: Parkinson’s disease; cell transplantation; dose-escalation study; efficacy study; human embryonic stem cells; midbrain dopaminergic neurons; preclinical study; safety study; stem-cell-based cell therapy.

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Conflict of interest statement

Declaration of interests D.-W.K. is a chief technology officer of S. Biomedics Co., Ltd. J.H.E., M.-Y.J., H.-J.H., S.K.C., S.T.N., K.-S.J., D.-H.K., C.-Y.P., and M.S.C. are currently employed at S. Biomedics Co., Ltd. We have patents related to this work. 1. Title: method for inducing differentiation of stem cells into dopaminergic neural precursor cells, patent number: 102392133(KR), 11655450(US), 07152050(JP), and 2020202273(AU). 2. Title: efficient and universal method for neural differentiation of human pluripotent stem cells, patent number: 101168053(KR), 08551783(US), 05756019(JP), and 02502987(EP).

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