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

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

    Neurology. 2019 Nov 18.

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

    Berry JD1, Cudkowicz ME1, Windebank AJ1, Staff NP1, Owegi M1, Nicholson K1, McKenna-Yasek D1, Levy YS1, Abramov N1, Kaspi H1, Mehra M1, Aricha R1, Gothelf Y1, Brown RH2.

    Author information
    1
    From Massachusetts General Hospital Neurological Clinical Research Institute and Harvard Medical School (J.D.B., M.E.C., K.N.), Boston; Mayo Clinic (A.J.W., N.P.S.), Rochester, MN; University of Massachusetts (M.O., D.M.-Y., R.H.B.), Worcester; Brainstorm Cell Therapeutics (Y.S.L., N.A., H.K., R.A., Y.G.), Petach Tikva, Israel; and Tigermed USA (M.M.), Somerset, NJ.
    2
    From Massachusetts General Hospital Neurological Clinical Research Institute and Harvard Medical School (J.D.B., M.E.C., K.N.), Boston; Mayo Clinic (A.J.W., N.P.S.), Rochester, MN; University of Massachusetts (M.O., D.M.-Y., R.H.B.), Worcester; Brainstorm Cell Therapeutics (Y.S.L., N.A., H.K., R.A., Y.G.), Petach Tikva, Israel; and Tigermed USA (M.M.), Somerset, NJ. robert.brown@umassmed.edu.
    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.

    https://www.ncbi.nlm.nih.gov/pubmed/31740545
    “As the cast of villains in SCI is vast and collaborative, so too must be the chorus of hero's that rise to meet them” Ramer et al 2005
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