{Reference Type}: Journal Article
{Title}: Preclinical and dose-ranging assessment of hESC-derived dopaminergic progenitors for a clinical trial on Parkinson's disease.
{Author}: Park S;Park CW;Eom JH;Jo MY;Hur HJ;Choi SK;Lee JS;Nam ST;Jo KS;Oh YW;Lee J;Kim S;Kim DH;Park CY;Kim SJ;Lee HY;Cho MS;Kim DS;Kim DW;
{Journal}: Cell Stem Cell
{Volume}: 31
{Issue}: 1
{Year}: 2024 01 4
{Factor}: 25.269
{DOI}: 10.1016/j.stem.2023.11.009
{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.