NurOwn, phase 2, randomized, clinical trial in patients with ALS: Safety, clinical, and biomarker results

James D. Berry, Merit E. Cudkowicz, Anthony J. Windebank, Nathan P. Staff, Margaret Owegi, Katherine Nicholson, Diane McKenna-Yasek, Yossef S. Levy, Natalie Abramov, Haggai Kaspi, Munish Mehra, Revital Aricha, Yael Gothelf, Robert H. Brown

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

ObjectiveTo 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.MethodsThe 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.ResultsThe 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).ConclusionA 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 evidenceThis phase II study provides Class I evidence.

Original languageEnglish (US)
Pages (from-to)E2294-E2305
JournalNeurology
Volume93
Issue number24
DOIs
StatePublished - Dec 10 2019

ASJC Scopus subject areas

  • Clinical Neurology

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    Berry, J. D., Cudkowicz, M. E., Windebank, A. J., Staff, N. P., Owegi, M., Nicholson, K., McKenna-Yasek, D., Levy, Y. S., Abramov, N., Kaspi, H., Mehra, M., Aricha, R., Gothelf, Y., & Brown, R. H. (2019). NurOwn, phase 2, randomized, clinical trial in patients with ALS: Safety, clinical, and biomarker results. Neurology, 93(24), E2294-E2305. https://doi.org/10.1212/WNL.0000000000008620