Overview: This study evaluated the safety and effectiveness of repeated intrathecal (injected into the spinal canal) administrations of autologous mesenchymal stem cells (multipotent stem cells found in bone marrow that are important for making and repairing skeletal tissues; MSC) in patients with amyotrophic lateral sclerosis (neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles; ALS).
Conclusion: Repeated intrathecal (injected into the spinal canal) administrations of autologous mesenchymal stem cells (multipotent stem cells found in bone marrow that are important for making and repairing skeletal tissues) were safe in patients with amyotrophic lateral sclerosis (neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles) and provided indications of medium-term benefits that were related to the intervals between the administration of the cells.
Background: Mesenchymal stem cells (MSC) were shown to induce beneficial effects in animal models of neurodegeneration and in pilot human trials in multiple sclerosis and amyotrophic lateral sclerosis (ALS). Aim: An open-label, clinical trial to evaluate the safety and efficacy of repeated intrathecal administrations of autologous-MSC in ALS-patients.
Methods: The study included 20 subjects (age: 20-70) with definite diagnosis of ALS and Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) score of >20. The patients were treated with 1-4 intrathecal injections of MSC, at intervals of 3-6 months. The primary endpoints were safety and tolerability. Efficacy measurements including ALSFRS-R score and forced vital capacity (FVC), were assessed as secondary endpoints.
Results: No serious adverse events were observed during the whole period of the trial. One patient withdrew from the study before the first injection. The monthly rate of progression in ALSFRS-R was ameliorated by more than 25% in 15/19 patients between the 1st and 2nd injection (mean improvement of 107.1%); in 11/12 between the 2nd and 3rd injection and in 8/10 between the 3rd and 4th injection. Overall, during the whole period till the last transplantation 13 patients had a >25% improvement in the slope of progression of ALSFRS-R (mean improvement of 47.4%, p < 0.0038, Wilcoxon rank signed test). 7 out of 19 patients actually improved clinically (range of increase in ALSFRS-R: +1 to +4 degrees) after the first transplantation and 5 remained improved after the second cycle. The response rate correlated with the time-intervals between the injections.
Conclusion: The results of our study show that repeated intrathecal injections of autologous MSC was safe in patients with ALS and provide indications of medium-term clinical benefits that were related to the intervals between the administrations of the cells. Larger studies are needed to confirm these observations.