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Repeated MSC Application Safe and Feasible for ALS Treatment



Review of “Phase I Trial of Repeated Intrathecal Autologous Bone Marrow-Derived Mesenchymal Stromal Cells in Amyotrophic Lateral Sclerosis” from Stem Cells TM by Stuart P. Atkinson

The neurodegenerative disorder Amyotrophic Lateral Sclerosis (ALS) currently lacks an effective treatment strategy, although stem cell therapy using mesenchymal stromal cells (MSCs) is an promising option for many researchers [1]. Mouse studies have found that intrathecal administrations of MSCs can prolong life span and slow disease progression [2] and some human clinical trials have found this intervention to be safe and feasible [3, 4]. Trials also suggested that repeated administration may improve clinical outcome [5], so to confirm this, the group of Seung Hyun Kim (Hanyang University, Seoul) have assessed safety during a 12-month follow-up period in a phase I clinical trial [6]. Encouragingly, they found that repeated administrations are safe and feasible, and support further late-stage clinical trials.

The group isolated autologous MSCs from the bone marrow and expanded these for 28 days. Seven ALS patients (3 male, 4 female) received intrathecal (within the arachnoid membrane of the brain) injections of autologous MSCs and then another 26 days later. During the subsequent 12 month follow up period, the researchers observed no serious adverse reactions, indicating that repeated injections were safe and feasible. The Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS-R) score, which measures the clinical impact of disease severity, found no acceleration in the mean rate of decline at 6 months, while analysis of the Appel ALS (AALS) and the forced vital capacity (FVC) scores found a similar lack of acceleration in the rate of decline. Finally, assessment of the cerebrospinal fluid (CSF) from two patients found increased levels of the cytokines IL-10, TGF-1, TGF-2, TGF-3, and IL-6, but a decrease in the chemokine-related MCP-1, known to worsen motor neuron injury in ALS.

This first clinical trial evaluating repeated intrathecal injections of autologous MSCs in ALS suggests that this therapeutic strategy is both safe and feasible. The authors do note limitations to their study, based on the lack of analysis of post mortem material and the small scale of the trial, both of which they hope to study further after the completion of an on-going phase II, controlled, randomized trial.

1. Mazzini L, Mareschi K, Ferrero I, et al. Mesenchymal stromal cell transplantation in amyotrophic lateral sclerosis: a long-term safety study. Cytotherapy 2012;14:56-60.
2. Kim H, Kim HY, Choi MR, et al. Dose-dependent efficacy of ALS-human mesenchymal stem cells transplantation into cisterna magna in SOD1-G93A ALS mice. Neuroscience letters 2010;468:190-194.
3. Karussis D, Karageorgiou C, Vaknin-Dembinsky A, et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 2010;67:1187-1194.
4. Prabhakar S, Marwaha N, Lal V, et al. Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis: a pilot study. Neurol India 2012;60:465-469.
5. Kim HY, Kim H, Oh KW, et al. Biological markers of mesenchymal stromal cells as predictors of response to autologous stem cell transplantation in patients with amyotrophic lateral sclerosis: an investigator-initiated trial and in vivo study. Stem Cells 2014;32:2724-2731.
6. Oh KW, Moon C, Kim HY, et al. Phase I trial of repeated intrathecal autologous bone marrow-derived mesenchymal stromal cells in amyotrophic lateral sclerosis. Stem Cells Translational Medicine 2015;4:590-597.