Intranasal human neural stem cell therapy in early-onset Parkinson’s disease with motor complications: A randomized, double-blind, placebo-controlled trial

Background: To evaluate the safety and efficacy of intranasal transplantation of ANGE-S003 human neural stem cells (hNSCs) in early-onset Parkinson’s disease (EOPD) patients with motor complications. Methods: In this randomized, double-blind, placebo-controlled trial, 24 EOPD patients were randomized (2:1) to receive weekly intranasal administrations of 1.5 × 107 hNSCs or placebo for 4 weeks, followed by 12 months of follow-up. The primary endpoint was change in MDS-UPDRS Part IV score at month 6. Results: No significant difference was observed in the primary endpoint (least-squares mean difference, 0.42; 95% CI, −4.29 to 5.13; P = 0.853). Controls showed greater worsening of off-state MDS-UPDRS Part III motor scores in non-onset limbs at 12 months (P = 0.029). Exploratory 11C-CFT PET analyses demonstrated greater reductions in dopaminergic activity in the non-onset caudate (P = 0.022) and anterior putamen (P = 0.045) in controls versus the treatment group. A total of 137 adverse events and 6 serious adverse events were reported. Conclusions: Although the primary endpoint was not met, motor and neuroimaging findings provide preliminary signals of a potential treatment effect. Larger studies are needed to confirm efficacy and safety.