Allogeneic Bone Marrow‐Derived Mesenchymal Stem Cells for Parkinson's Disease: A Randomized Trial

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.