(searched for: doi:10.1212/*)
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Neurology, Volume 93, pp 945.2-946; doi:10.1212/wnl.0000000000008528
Neurology, Volume 93, pp 931-931; doi:10.1212/wnl.0000000000008526
Abstract: Objective To determine the safety and efficacy of mesenchymal stem cell (MSC)-neurotrophic factor (NTF) cells (NurOwn®, autologous bone marrow-derived MSCs, induced to secrete NTFs) delivered by combined intrathecal and intramuscular administration to participants with amyotrophic lateral sclerosis (ALS) in a phase 2 randomized controlled trial.Methods The study enrolled 48 participants randomized 3:1 (treatment: placebo). After a 3-month pretransplant period, participants received 1 dose of MSC-NTF cells (n = 36) or placebo (n = 12) and were followed for 6 months. CSF was collected before and 2 weeks after transplantation.Results The study met its primary safety endpoint. The rate of disease progression (Revised ALS Functional Rating Scale [ALSFRS-R] slope change) in the overall study population was similar in treated and placebo participants. In a prespecified rapid progressor subgroup (n = 21), rate of disease progression was improved at early time points (p < 0.05). To address heterogeneity, a responder analysis showed that a higher proportion of treated participants experienced ≥1.5 points/month ALSFRS-R slope improvement compared to placebo at all time points, and was significant in rapid progressors at 4 and 12 weeks (p = 0.004 and 0.046, respectively). CSF neurotrophic factors increased and CSF inflammatory biomarkers decreased in treated participants (p < 0.05) post-transplantation. CSF monocyte chemoattractant protein-1 levels correlated with ALSFRS-R slope improvement up to 24 weeks (p < 0.05).Conclusion A single-dose transplantation of MSC-NTF cells is safe and demonstrated early promising signs of efficacy. This establishes a clear path forward for a multidose randomized clinical trial of intrathecal autologous MSC-NTF cell transplantation in ALS.Classification of evidence This phase II study provides Class I evidence.
Neurology, Volume 93, pp 930-930; doi:10.1212/wnl.0000000000008524
Neurology, Volume 93; doi:10.1212/wnl.0000000000008530
Neurology, Volume 93, pp 911-918; doi:10.1212/wnl.0000000000008527
Neurology, Volume 93, pp 939-944; doi:10.1212/wnl.0000000000008535
Neurology, Volume 93, pp 946-947; doi:10.1212/wnl.0000000000008531
Neurology, Volume 93, pp 945.1-945; doi:10.1212/wnl.0000000000008529