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

• DOI: 10.1016/j.stem.2023.11.009
• Publication Date: 2023-12-11T15:38:03Z
• Authors: Sanghyun Park; Chan Wook Park; Jang Hyeon Eom; Mi-Young Jo; Hye-Jin Hur; Sung Kyoung Choi; Jae Souk Lee; Seung Taek Nam; Ki-Sang Jo; Young Woo Oh; Jungil Lee; Sieun Kim; Do-Hun Kim; Chul-Yong Park; Su Jin Kim; Ho-Young Lee; Myung Soo Cho; Dae-Sung Kim; Dong-Wook Kim

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.