Objective: To evaluate longitudinal changes in global cognition following intravenous allogeneic bone marrow–derived mesenchymal stem cell (allo-hBM-MSC) therapy in Parkinson’s disease (PD).

Background: Cognitive impairment is a common feature of PD, with dementia risk increasing to 27% at 10 years, 50% at 15 years, and 74% at 20 years after diagnosis.[1] Global cognition declines by approximately 0.5 points per year on the Montreal Cognitive Assessment (MoCA) in longitudinal PD cohorts.[2] No therapies have demonstrated consistent effects on cognitive trajectories. Mesenchymal stem cells (MSCs) possess immunomodulatory and neurotrophic properties that may influence neurodegeneration [3]

Method: Cognitive outcomes were examined in a prespecified secondary analysisfrom a randomized, double-blind Phase IIa trial of intravenous allo-hBM-MSCs in patients with mild-to-moderate PD (Hoehn & Yahr ≤3). Participants with baseline MoCA scores <25 were excluded. Individuals were randomized (1:1:1) to receive three placebo infusions, one placebo followed by two allo-hBM-MSC infusions, or three allo-hBM-MSC infusions  every 18 weeks (10×10⁶ cells/kg per infusion). MoCA total score was assessed at baseline, Week 49, and Week 88. Longitudinal change was analyzed using Bayesian generalized linear mixed-effects models.

Results: Forty-five participants were randomized (three infusions, n = 16; two infusions, n = 14; placebo, n = 15), and 40 (89%) completed the 88-week follow-up. Baseline cognition was comparable across groups. By Week 88, mean differences in MoCA score relative to placebo were +1.03 points (posterior probability [PP] = 86.5%) in the three-infusion arm and +1.45 points (PP = 93.4%) in the two-infusion arm [Table 1]. Longitudinal modeling demonstrated corresponding differences in cognitive trajectories, with estimated annual changes of +0.215 points in the three-infusion group and +0.428 points in the two-infusion group, compared with −0.247 points per year in the placebo group [Figure 1].

Conclusion: In patients with mild-to-moderate PD and preserved baseline cognition, repeated intravenous allo-hBM-MSC infusions were associated with relative preservation of global cognition over 88 weeks relative to placebo. Larger trials powered for cognitive outcomes are needed to determine whether MSC therapy alters cognitive trajectories in PD.

Figure 1

Table 1

References: [1] Gallagher J, et al. Long-term risk of dementia in Parkinson disease. Neurology. 2024;103(5):e209699.
[2] Hu MT, et al. Predictors of cognitive impairment in an early stage Parkinson’s disease cohort. Mov Disord. 2014;29(3):351–359
[3] Schiess M, Suescun J, Doursout MF, Adams C, Green C, Saltarrelli JG, Savitz S, Ellmore TM. Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Safety in Idiopathic Parkinson’s Disease. Mov Disord. 2021 Aug;36(8):1825-1834.

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/preservation-of-cognition-following-intravenous-mesenchymal-stem-cell-therapy-in-parkinsons-disease-secondary-analysis-of-a-randomized-trial/