Advanced science (Weinheim, Baden-Wurttemberg, Germany)Jul 6, 2026

Fixing a Gene Improves Dopamine Cell Therapy in a Monkey Model of Parkinson's Disease

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 7, 2026

Abstract

Over 18 months, grafted dopaminergic progenitor cells survived and exhibited mature properties in primate models.

Isogenic human induced pluripotent stem cell lines were generated from a Parkinson's disease patient with specific LRRK2 mutations.
Both mutant and gene-corrected progenitor cells were transplanted into the brains of monkeys with induced Parkinson's-like symptoms.
Imaging showed restored dopamine synthesis in both groups, with no significant differences in outcomes between mutant and corrected cells.
Behavioral tests indicated sustained motor improvements and increased exploratory behavior in the monkeys post-transplantation.
No tumor formation or adverse reactions were noted, and overall safety markers in the monkeys remained normal.

Simplified

Human induced pluripotent stem cell (iPSC)-derived dopaminergic progenitors offer a promising strategy for cell replacement in Parkinson's disease (PD), yet their long-term efficacy and safety in primates remain underexplored. Here, we generated isogenic iPSC lines from a PD patient carrying compound LRRK2 mutations (R50H and M2397T) and used CRISPR/Cas9 and prime editing to correct these variants. Both mutant and gene-corrected lines were differentiated into midbrain dopaminergic progenitors (DA-NPCs), characterized in vitro, and transplanted bilaterally into the striatum of MPTP-lesioned cynomolgus monkeys. Over 18 months, grafted cells survived, expressed TH and GIRK2, and exhibited mature electrophysiological properties. [¹ ⁸F] DOPA PET imaging revealed restored dopamine synthesis in both grafting groups, with no statistically significant differences observed between mutant and gene-corrected groups. Behavioral assessments showed sustained motor improvements and enhanced exploratory behavior. No tumor formation or adverse astrocytic response was observed, and systemic safety markers remained normal. These findings demonstrate that both mutant and corrected DA-NPCs integrate and function in the primate brain. Our results support the feasibility of personalized regenerative therapies for genetic PD.