Accès ouvert déclaré 2022 preprint

Foetal Allogeneic Intracerebroventricular Neural Stem Cell Transplantation in People with Secondary Progressive Multiple Sclerosis: A phase I dose-escalation clinical trial

Maurizio Angelo Leone, Maurizio Gelati, DC Profico, C Conti, Cristina Spera, Gianmarco Muzi, Valentina Grespi, Ilaria Bicchi, Claudia Ricciolini, Daniela Ferrari, Michele M. Zarrelli, Luigi Amoruso, Giuliana Placentino, Paola Crociani, F. Apollo, Pietro Di Viesti, Danilo Fogli, Teresa Popolizio, Carlo Colosimo, Domenico Frondizi, G Stipa, E Tinella, A Ciampini, S Sabatini, F Paci, Giada Silveri, Claudio Gobbi, Emanuele Pravatà, E Zecca, RF Balzano, Jens Kühle, Massimiliano Copetti, Andrea Fontana, Massimo Carella, G D’Aloisio, L Abate, Yendry Ventura‐Carmenate, Stefano Pluchino, Luca Peruzzotti‐Jametti, AL Vescovi

3Citations signalées, ce qui n’est pas une note de qualité

8Institutions déclarées

3Pays d’affiliation déclarés

Rattachement africain : it, ch, gb. Niveau de preuve : code pays fourni par la source.

Le résumé fourni par la source

ABSTRACT Background Advanced cell therapeutics are emerging as potentially effective treatments for chronic neurological diseases, including secondary progressive multiple sclerosis (SPMS). Here we report the results of a phase I trial in which good manufacturing practice-grade foetal allogeneic human neural stem cells (hNSCs) were implanted via intracerebroventricular (ICV) injection in 15 individuals with active and non-active SPMS. Methods This is a phase I, open-label, multicentre, dose-escalation, international study. The primary objective was to assess the feasibility, safety, and tolerability of ICV injections of allogeneic hNSCs in patients affected by SPMS over a study follow up of 12 months. We also evaluated the number and type of adverse events (AEs) leading to a maximum tolerated dose, the general health status, and mortality. The secondary objectives were the therapeutic benefit of allogeneic hNSCs using assessment scales, magnetic resonance imaging (MRI), and laboratory and neurophysiologic parameters. Findings Fifteen unrelated SPMS patients were enrolled and treated between 2018 and 2020. The participants had a median age of 49.8 years. Their mean extended disability status scale (EDSS) at enrolment was 7.6, the mean disease duration was 22 years, and mean time from diagnosis to progression was 10.1 years. Neither treatment-related deaths nor serious AEs were reported during the study (1 year follow up after treatment). All the other AEs were classified as non-serious and were associated to non-study concomitant therapy or other medical conditions not connected to the experimental treatment. During the study, none of the participants worsened in the progression of their SPMS as shown by the evaluation scales implemented to assess their progress. Laboratory and neurophysiologic parameters showed no clinically significant variations. MRI follow-up showed non-clinically significant type 1, 2, and 3 changes. Interpretation The intracerebroventricular injection of foetal allogeneic hNSCs in people with SPMS is feasible, tolerated and safe. Study participants displayed a substantial clinical stability during the 12-month follow-up. The absence of relevant adverse reactions (Ars) arising from the transplantation of hNSCs indicates a short-term neutral balance between benefits and risks and suggests a concrete, though perspective therapeutic possibility for SPMS patients. Further studies are needed to confirm and extend the findings herein and evaluate the actual therapeutic potential of advanced cell therapeutics for a condition where the lack of effective disease modifying therapies is a major unmet clinical need.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.

Le contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref: Foetal Allogeneic Intracerebroventricular Neural Stem Cell Transplantation in People with Secondary Progressive Multiple Sclerosis: A phase I dose-escalation clinical trial
Date Crossref: 15/11/2022
Éditeur: openRxiv
Type: posted-content

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.

Où se fait cette recherche

Casa Sollievo della Sofferenza pays non établi dans la notice
Établissement de santé
Istituti di Ricovero e Cura a Carattere Scientifico pays non établi dans la notice
Établissement de santé
University of Milano-Bicocca pays non établi dans la notice
Université ou école supérieure
Laboratory for Biomedical Neurosciences pays non établi dans la notice
Structure de recherche
Università della Svizzera italiana pays non établi dans la notice
Université ou école supérieure
University of Basel pays non établi dans la notice
Université ou école supérieure
University Hospital of Basel pays non établi dans la notice
Établissement de santé
University of Cambridge Department of Clinical Neurosciences and NIHR Biomedical Research Centre pays non établi dans la notice
Université ou école supérieure
AOSP Santa Maria pays non établi dans la notice
Institution
BTBS Università Bicocca pays non établi dans la notice
Institution
Faculty of biomedical Sciences pays non établi dans la notice
Université ou école supérieure
Multiple Sclerosis Centre (MSC) pays non établi dans la notice
Institution

Casa Sollievo della Sofferenza, Istituti di Ricovero e Cura a Carattere Scientifico et University of Milano-Bicocca, avec 9 autres affiliations.

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

Multiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanismsMesenchymal stem cell research

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