Repeated Intrathecal Mesenchymal Stem Cells for Amyotrophic Lateral Sclerosis
Ki-Wook Oh, Min-Young Noh, Min-Soo Kwon, Hyun Young Kim, Seong-Il Oh, Jinseok Park, Hee-Jin Kim, Chang-Seok Ki, Seung Hyun Kim, Ki-Wook Oh, Min-Young Noh, Min-Soo Kwon, Hyun Young Kim, Seong-Il Oh, Jinseok Park, Hee-Jin Kim, Chang-Seok Ki, Seung Hyun Kim
Abstract
Objective: To assess the safety and efficacy of 2 repeated intrathecal injections of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in amyotrophic lateral sclerosis (ALS).
Methods: In a phase 2 randomized controlled trial (NCT01363401), 64 participants with ALS were randomly assigned treatments (1:1) of riluzole alone (control group, n = 31) or combined with 2 BM-MSC injections (MSC group, n = 33). Safety was assessed based on the occurrence of adverse events. The primary efficacy outcome was changes in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score from baseline to 4 and 6 months postinjection. Post hoc analysis includes investigation of cerebrospinal fluid biomarkers and long-term survival analysis.
Results: Safety rating showed no groupwise difference with absence of serious treatment-related adverse events. Mean changes in ALSFRS-R scores from baseline to 4 and 6 months postinjection were reduced in the MSC group compared with the control group (4 months: 2.98, 95% confidence interval [CI] = 1.48-4.47, p < 0.001; 6 months: 3.38, 95% CI = 1.23-5.54, p = 0.003). The MSC group showed decreased proinflammatory and increased anti-inflammatory cytokines. In good responders, transforming growth factor β1 significantly showed inverse correlation with monocyte chemoattractant protein-1. There was no significant difference in long-term survival between groups.
Interpretation: Repeated intrathecal injections of BM-MSCs demonstrated a possible clinical benefit lasting at least 6 months, with safety, in ALS patients. A plausible action mechanism is that BM-MSCs mediate switching from pro- to anti-inflammatory conditions. A future randomized, double-blind, large-scale phase 3 clinical trial with additional BM-MSC treatments is required to evaluate long-term efficacy and safety. Ann Neurol 2018;84:361-373.
© 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
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Source: PubMed