Clinical and Immunologic Safety Evaluation of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells in Parkinson’s Disease
Chiamaka Onuigbo1, Jerome Saltarrelli1, Juan Martinez Lemus1, Emily Tharp1, Scott Olson1, Fabio Triolo1, Joana Bianchi1, Robert Ritter III1, Mya Schiess1
1University of Texas Health Sciences Center at Houston
Objective:
To evaluate the safety of intravenous (IV) allogeneic bone marrow-derived mesenchymal stem cells (allo-hMSCs) in Parkinson’s disease (PD) across Phase I and Phase II clinical trials.
Background:
Mesenchymal stem cells (MSCs) have neuroprotective and immunomodulatory properties, making them a promising therapy for PD. However, safety profiles in PD remain limited, especially regarding repeated infusions and potential antibody-mediated rejection.
Design/Methods:
Both trials enrolled participants with mild to moderate PD, aged 45-79, OFF-state Hoehn and Yahr stage £ 3, and 4-10 year disease duration. Phase I (n=20) tested single escalating IV infusions of 1, 3, 6, or 10 x 106 MSCs/kg. Phase II (n = 30) administered either three infusions of 10 x 106 MSCs/kg or two MSC infusions plus one placebo every 18 weeks. No pre-treatment was used. Adverse events (AEs), HLA profiles, and calculated panel reactive antibody (cPRA) values were recorded at prespecified intervals.
Results:
Across both trials, 215 AEs were reported; 10 AEs (4.7%) were treatment-related. Of these, 8 were mild, 1 moderate, and 1 severe. Common AEs included dyskinesia (30%), nausea (20%), and lymphocytic changes (20%). The single severe AE was a new diagnosis of chronic lymphocytic leukemia in a participant with pre-existing stable lymphocytosis, which eventually stabilized. Twenty-eight participants (56%) had stable or reduced cPRA values. Transient increases occurred in 8 (16%), and sustained increases with new HLA specificities in 6 (12%), only from Phase II. New HLA specificities emerged in 8 participants (16%) without cPRA changes. Sensitization showed a nonsignificant trend towards higher sustained increase in Phase II (p = 0.09). No donor-specific antibodies were detected.
Conclusions:
Single and repeated IV MSC infusions are safe and well tolerated. Although multiple dosing increased the sensitization risk, most participants remained at low cPRA, supporting a favorable safety and immunologic profile for allo-hMSC therapy in PD.
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