Objective: Prove safety and feasibility of delivering allogeneic bone marrow-derived mesenchymal stem cells (MSC) intravenously in escalated doses to patients with idiopathic Parkinson’s disease (PD).

Background: Neuroinflammation plays a crucial role in the pathogenesis of PD, supporting the rationale for using MSC as immunomodulatory therapy for restoring homeostasis to the neuronal-glial microenvironment.

Method: 12-month single-center open-label dose-escalation phase 1 study. 20 subjects with mild/moderate PD were sequentially assigned to one of four doses: 1, 3, 6, or 10 X 10⁶MSCs/kg given as a single intravenous infusion; Groups A,B,C,D respectively and evaluated at 3, 12, 24, and 52 weeks post-infusion. Primary outcome safety measures were absence of immediate transfusion reaction, study-related adverse events, organ damage or immunogenic reactions. Secondary outcomes were therapy’s impact on peripheral markers, PD progression, and changes in brain perfusion.

Results: Baseline characteristics appeared similar across groups except for cognition (p<0.05) [Table 1]. Twenty subjects received a single IV infusion; during the first 24 hours post-infusion, three patients reported transient treatment-emergent adverse events (TEAEs), one phlebitis, one antecubital fossa hematoma, and one headache.  Most common TEAEs were dyskinesias (25%, N=5) and hypertension (20%, N=4). One study SAE happened in a patient with a 4-year history of lymphocytosis who developed asymptomatic chronic lymphocytic leukemia [Table 2]. There was no response to donor HLA over the 12-month study. At 52 weeks CCL2 declined 15% (p<0.01), CCL22 29% (p<0.05), along with an increase in BDNF 46% (p<0.05). The highest dose had the most significant effect on reducing OFF UPDRS motor -14.4 (p<0.01) and total scores (-20.8, p<0.001) [Figure 1]. Main effects of time and region (p<0.001) on brain perfusion occurred with a significant increase in the subthalamic nucleus (p=0.042) at 24 weeks.

Conclusion: This study demonstrates that a single infusion of allogeneic MSC is safe and well-tolerated in mild/moderate PD patients. Our data points towards a treatment effect that relies on peripheral immune modulation. There is a potential signal for clinical improvement, but this should be interpreted with caution based on both the limited sample size and the purpose of the study.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/allogeneic-bone-marrow-derived-mesenchymal-stem-cells-safety-and-tolerability-in-idiopathic-parkinsons-disease/