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

Adult Aged Amyotrophic Lateral Sclerosis / therapy Double-Blind Method Female Humans Male Mesenchymal Stem Cell Transplantation / methods Middle Aged Nerve Growth Factors / cerebrospinal fluid Transplantation, Autologous

Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
10 12 2019
Historique:
received: 30 01 2019
accepted: 30 07 2019
pubmed: 20 11 2019
medline: 8 2 2020
entrez: 20 11 2019
Statut: ppublish

Résumé

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. 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. 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 ( 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. This phase II study provides Class I evidence.

Identifiants

DOI: 10.1212/WNL.0000000000008620 PMID: 31740545 PMC: PMC6937497
pubmed: 31740545
pii: WNL.0000000000008620
doi: 10.1212/WNL.0000000000008620
pmc: PMC6937497
doi:

Substances chimiques

Nerve Growth Factors 0

Types de publication

Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2294-e2305

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

James D Berry (JD)

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.

Merit E Cudkowicz (ME)

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.

Anthony J Windebank (AJ)

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.

Nathan P Staff (NP)

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.

Margaret Owegi (M)

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.

Katherine Nicholson (K)

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.

Diane McKenna-Yasek (D)

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.

Yossef S Levy (YS)

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.

Natalie Abramov (N)

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.

Haggai Kaspi (H)

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.

Munish Mehra (M)

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.

Revital Aricha (R)

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.

Yael Gothelf (Y)

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 H Brown (RH)

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.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › NurOwn, phase 2, randomized, clinical trial in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › NurOwn, phase 2, randomized, clinical trial in...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles de l'homéostasie des protéines › Protéinopathies TDP-43 › Sclérose latérale amyotrophique › NurOwn, phase 2, randomized, clinical trial in...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › NurOwn, phase 2, randomized, clinical trial in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › NurOwn, phase 2, randomized, clinical trial in...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation de cellules souches › Transplantation de cellules souches mésenchymateuses › NurOwn, phase 2, randomized, clinical trial in...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › NurOwn, phase 2, randomized, clinical trial in...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteurs de croissance nerveuse › NurOwn, phase 2, randomized, clinical trial in...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation autologue › NurOwn, phase 2, randomized, clinical trial in...