AUTHOR=Agüera-Morales Eduardo , Fernández-Sánchez Victoria Eugenia , Navarro-Mascarell Guillermo , Cabezas-Rodríguez Juan Antonio , Peña-Toledo María Ángeles , Reyes-Rodríguez Virginia , Postigo-Pozo María José , Patrignani-Ochoa Giorgio , Geniz-Clavijo María Ángeles , Márquez-Infante Celedonio , Tallon-Aguilar Luis , Tinoco-González José , Padillo-Ruiz Javier , Valladares-Sánchez Amador , Caballero-Eraso Candela , López-Ramírez Cecilia , Mata Alcázar-Caballero Rosario , Leyva-Fernández Laura , Rodríguez-Acosta Antonio , Maldonado-Sánchez Rafael , García-Martín María Luisa , Somoza-Ramírez MªLuisa , Quijano-Ruiz Blanca , Macías-Sánchez María del Mar , Carmona-Sánchez Gloria , Fernández-López Olga , Fernández-Fernández Óscar 

TITLE=Adipose-derived mesenchymal stem cells for the treatment of Amyotrophic Lateral Sclerosis. A phase I/II safety and efficacy clinical trial

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1655124

DOI=10.3389/fneur.2025.1655124

ISSN=1664-2295

ABSTRACT=IntroductionAmyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with few treatments available. Mesenchymal stem cells have arisen as a potential treatment option for ALS due to their immune system modulation and their neuroprotective effects. This clinical trial aimed to evaluate the safety, efficacy and feasibility of three intravenous doses of autologous adipose-derived mesenchymal stem cells (AdMSC) in ALS patients.MethodsA multicentre, randomized, parallel group, placebo-controlled, double-blinded clinical trial (EudraCT: 2011-006254-85) was conducted in 40 patients with ALS in treatment with riluzole. Patients were randomized 1:1:1:1 into the following treatment groups: 1 × 106 cells/kg, 2 × 106 cells/kg, 4 × 106 cells/kg and placebo. After a 6 month follow-up, patients in the placebo group were randomized 1:1:1 to receive one of the three doses of AdMSC and they were followed up for another 6 months. Lastly, all patients were followed-up in a 36-month open-label extension. Safety was mainly assessed through the evaluation of adverse events and their relationship with the medicinal product. Several variables were measured to assess efficacy, such as ALS Functional Rating Scale, Ashworth spasticity scale, neurophysiological and neuropsychological parameters and overall survival. The feasibility of the procedure was assessed through the evaluation of the extraction and infusion of AdMSC.ResultsSafety of AdMSC was observed through all follow-up periods, with similar percentages of adverse events between groups and no significant differences between groups in the rate of adverse events related to treatment. The administration procedure was feasible for all patients. Across all analyzed measures, we observed the expected progressive decline characteristic of ALS, with no statistically significant between-group differences in the rate of change.DiscussionThe results obtained in this study are consistent with the ones obtained in other clinical trials using similar doses of MSC, where safety was demonstrated and efficacy results were inconclusive, due to not reaching statistical significance. Larger studies with an increased sample size, different doses and route of administration or combination of routes, repeated dosing or larger duration and comprehensive assessment of immunological effect would be needed to analyze the efficacy of AdMSC in the treatment of ALS.Clinical trial registrationhttps://www.clinicaltrialsregister.eu/ctr-search/search?query=2011-006254-85.