Abstract
BACKGROUND: Neuroinflammation contributes to Parkinson's disease (PD) progression and motor dysfunction. Allogeneic human mesenchymal stem cells (allo-hMSCs) may reduce neuroinflammation and improve motor symptoms. OBJECTIVES: To evaluate the efficacy of repeated intravenous doses of 10 × 10(6)/kg allo-hMSCs in improving motor symptoms in patients with PD (PwP). METHODS: In this phase 2, randomized, placebo-controlled trial (November 2020-July 2023), mild-to-moderate PwP received either three allo-hMSC infusions, one placebo followed by two allo-hMSC infusions, or three placebo infusions at 18-week intervals. Follow-up lasted 88 weeks. The primary outcome was a >70% posterior probability (PP) of a difference in the proportion of participants with ≥5-point improvement in OFF-medication Movement Disorder Society Sponsored Revision of the Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III) at week 62. Bayesian analysis was conducted using R v4.2.0. RESULTS: Forty-five PwP were enrolled. A larger proportion of subjects achieved a ≥5-point improvement in MDS-UPDRS-III in the three-infusion arm compared with placebo at week 62 (mean difference [MD]: 5.0%, PP = 93.7%), translating to a 16.9-point improvement in MDS-UPDRS-III in the three-infusion arm compared with a 14.6-point improvement in the placebo arm. Conversely, fewer subjects in the two-infusion arm compared with placebo showed ≥5-point improvement at week 62 (MD: -62.4%, PP ≥ 99.9%), translating to only a 3.9-point improvement in MDS-UPDRS-III in the two-infusion arm. However, improvement in MDS-UPDRS-III was seen across all treatment arms. Adverse events were mild and transient. CONCLUSIONS: Three infusions of 10 × 10(6) allo-hMSCs/kg improved motor function in mild-to-moderate PwP, while two infusions showed less improvement than placebo. To address this discrepancy, future studies should conduct functional potency assays to understand batch-to-batch variability affecting clinical efficacy. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.