Objective: Assess the impact of treatment with intravenous (IV) allogeneic bone marrow-derived mesenchymal stem cells (allo-hMSCs) on cognition in patients with mild-moderate Parkinson’s Disease (PD).

Background: Parkinson’s Disease Dementia affects up to 31% of patients, with nearly half developing dementia within 10 years of diagnosis [1]. PD patients at high risk of dementia show greater activation of the innate immune system compared to those at lower risk [2]. Immunomodulatory therapies, such as mesenchymal stem cells, may help prevent cognitive decline in patients with PD (PwPD) [3].

Method: In this randomized, double-blind, placebo-controlled Phase 2 trial [4], we enrolled individuals aged 50–79 with mild-to-moderate Parkinson’s disease (Hoehn & Yahr stages 1–3, disease duration of 2–10 years) and a Montreal Cognitive Assessment (MoCA) score >26. Participants were randomly assigned to one of three groups: (1) three intravenous (IV) infusions of 10×10⁶ allo-hMSCs/kg (N=16), (2) one IV placebo infusion followed by two IV infusions of 10×10⁶ allo-hMSCs/kg (N=14), or (3) three IV placebo infusions (N=15). Infusions were administered 18 weeks apart. Cognitive impairment was assessed using the MoCA at baseline and at week 88. A Bayesian analysis compared the mean differences in MoCA scores between the active treatment groups and the placebo group at week 88, adjusting for baseline scores as a covariate. Data were analyzed using R v4.2.0.

Results: Of the 45 participants enrolled, 40 completed the week 88 follow-up (figure1). Baseline motor severity scores and cognitive function were similar across study arms [table1]. Compared to placebo, the mean MoCA score significantly increased in the three allo-hMSC infusion arm (Mean Difference [MD]: 0.7, Credible Interval [CrI]: -0.47 to 1.99, Posterior Probability [PP]: 89.2%) and the two allo-hMSC infusion arm (MD: 0.9, CrI: -0.3 to 2.1, PP: 93.2%) [figure 1].

Conclusion: Repeated infusions of mesenchymal stem cells have been shown to improve cognitive performance in PwPD without dementia, suggesting a potential therapy to slow cognitive decline in PwPD. Larger trials are necessary to validate this efficacy in PwPD with and without dementia.

Table 1

Figure 1

References: [1] Aarsland D, Batzu L, Halliday GM, Geurtsen GJ, Ballard C, Ray Chaudhuri K, Weintraub D. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers. 2021 Jul 1;7(1):47. doi: 10.1038/s41572-021-00280-3. Erratum in: Nat Rev Dis Primers. 2021 Jul 13;7(1):53. doi: 10.1038/s41572-021-00292-z. PMID: 34210995.

[2] Wijeyekoon RS, Kronenberg-Versteeg D, Scott KM, Hayat S, Kuan WL, Evans JR, Breen DP, Cummins G, Jones JL, Clatworthy MR, Floto RA, Barker RA, Williams-Gray CH. Peripheral innate immune and bacterial signals relate to clinical heterogeneity in Parkinson’s disease. Brain Behav Immun. 2020 Jul;87:473-488. doi: 10.1016/j.bbi.2020.01.018. Epub 2020 Jan 30. PMID: 32006615; PMCID: PMC7613010.

[3] Zhang X, Hou X, Te L, Zhongsheng Z, Jiang J, Wu X. Mesenchymal stem cells and exosomes improve cognitive function in the aging brain by promoting neurogenesis. Front Aging Neurosci. 2022 Oct 18;14:1010562. doi: 10.3389/fnagi.2022.1010562. PMID: 36329874; PMCID: PMC9623286.

[4] ClinicalTrials.gov. Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Idiopathic Parkinson’s Disea [Internet]. Bethesda (MD): National Library of Medicine (US); 2023 [cited 2025 Feb 26]. Available from: https://clinicaltrials.gov/study/NCT02611167

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cognitive-improvement-in-parkinsons-disease-patients-after-intravenous-mesenchymal-stem-cell-infusion-results-from-a-phase-2-randomized-trial/