Abstract
Background: This study aimed to investigate the safety and tolerability of the intra-arterial administration of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with multiple system atrophy (MSA)-cerebellar type (MSA-C).Methods: This was a single-center, open-label phase I clinical trial in patients with MSA-C. A three-stage dose escalation scheme (low-dose, 3.0 × 105 cells/kg; medium-dose, 6.0 × 105 cells/kg; high-dose, 9.0 × 105 cells/kg) was applied to determine the maximum tolerated dose of intra-arterial administration of BM-MSCs based on the no-observed-adverse-effect level derived from the toxicity study. The occurrence of adverse events was evaluated 1 day before and 1, 14, and 28 days after BM-MSC therapy. Additionally, we assessed changes in the Unified MSA Rating Scale (UMSARS) score 3 months after BM-MSC treatment.Results: One serious adverse drug reaction (ADR) of leptomeningeal enhancement following the intra-arterial BM-MSC administration occurred in one patient in the low-dose group. The safety review of the Internal Monitoring Committee interpreted this as radiological evidence of the blood-brain barrier permeability for MSCs. No other ADRs were observed in the medium- or high-dose groups. In particular, no ischemic lesions on diffusion-weighted images were observed in any of the study participants. Additionally, the medium- and high-dose groups tended to show a slower increase in UMSARS scores than the low-dose group during the 3-month follow-up.Conclusions: The present study confirmed that a single intra-arterial administration of autologous BM-MSCs is a safe and promising neuroprotective strategy in patients with MSA-C.Trial registration: This trial was registered at http://www.clinicaltrials.gov as #NCT03265444. Registered 29 August 2017, https://clinicaltrials.gov/ct2/show/NCT03265444?term=NCT03265444.&draw=2&rank=1.
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