Stem cell therapy is an emerging alternative therapeutic or disease-modifying strategy for amyotrophic lateral sclerosis (ALS). The aim of this open-label phase I clinical trial was to evaluate the safety of two repeated intrathecal injections of autologous bone marrow (BM)-derived mesenchymal stromal cells (MSCs) in ALS patients. Eight patients with definite or probable ALS were enrolled. After a 3-month lead-in period, autologous MSCs were isolated two times from the BM at an interval of 26 days and were then expanded in vitro for 28 days and suspended in autologous cerebrospinal fluid. Of the 8 patients, 7 received 2 intrathecal injections of autologous MSCs (1 3 10 6 cells per kg) 26 days apart. Clinical or laboratory measurements were recorded to evaluate the safety 12 months after the first MSC injection. The ALS Functional Rating Scale-Revised (ALSFRS-R), the Appel ALS score, and forced vital capacity were used to evaluate the patients' disease status. One patient died before treatment and was withdrawn from the study. With the exception of that patient, no serious adverse events were observed during the 12-month follow-up period. Most of the adverse events were self-limited or subsided after supportive treatment within 4 days. Decline in the ALSFRS-R score was not accelerated during the 6-month follow-up period. Two repeated intrathecal injections of autologous MSCs were safe and feasible throughout the duration of the 12-month follow-up period. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:590-597

ObjectiveTo assess the safety and efficacy of 2 repeated intrathecal injections of autologous bone marrow–derived mesenchymal stem cells (BM‐MSCs) in amyotrophic lateral sclerosis (ALS).MethodsIn a phase 2 randomized controlled trial (NCT01363401), 64 participants with ALS were randomly assigned treatments (1:1) of riluzole alone (control group, n = 31) or combined with 2 BM‐MSC injections (MSC group, n = 33). Safety was assessed based on the occurrence of adverse events. The primary efficacy outcome was changes in Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised (ALSFRS‐R) score from baseline to 4 and 6 months postinjection. Post hoc analysis includes investigation of cerebrospinal fluid biomarkers and long‐term survival analysis.ResultsSafety rating showed no groupwise difference with absence of serious treatment‐related adverse events. Mean changes in ALSFRS‐R scores from baseline to 4 and 6 months postinjection were reduced in the MSC group compared with the control group (4 months: 2.98, 95% confidence interval [CI] = 1.48–4.47, p < 0.001; 6 months: 3.38, 95% CI = 1.23–5.54, p = 0.003). The MSC group showed decreased proinflammatory and increased anti‐inflammatory cytokines. In good responders, transforming growth factor β1 significantly showed inverse correlation with monocyte chemoattractant protein‐1. There was no significant difference in long‐term survival between groups.InterpretationRepeated intrathecal injections of BM‐MSCs demonstrated a possible clinical benefit lasting at least 6 months, with safety, in ALS patients. A plausible action mechanism is that BM‐MSCs mediate switching from pro‐ to anti‐inflammatory conditions. A future randomized, double‐blind, large‐scale phase 3 clinical trial with additional BM‐MSC treatments is required to evaluate long‐term efficacy and safety. Ann Neurol 2018;84:361–373

The results of this study showed that microglia functional properties may be modulated depending on the composition and quantity of mesenchymal stromal cell (MSC)-secreting factors. Transforming growth factor (TGF)-β is proposed as a modulator of microglia functional properties among MSC-secreting factors, and this study aligns with a previous clinical study by these same authors. TGF-β releasing capacity could be an important factor enhancing the therapeutic efficacy of MSCs in clinical trials.

ObjectiveThis study aimed to determine the incidence, prevalence and survival time of Korean patients with amyotrophic lateral sclerosis (ALS) using National Health Insurance Service (NHIS) data.MethodsUsing NHIS data, the Korean nationwide health dataset, we identified patients with motor neuron diseases who were first diagnosed with a KCD-6 code (G12.20–G12.28; modified from ICD-10 codes) between 2011 and 2015. ALS (G12.21 code) epidemiological characteristics, including annual incidence, prevalence, mortality rates and survival time, were analysed and compared with sociodemographic variables.ResultsNew patients with ALS (n=3049) were enrolled over 5 years. The mean annual incidence was 1.20/100 000, and the sex ratio was 1.60 (male:female). The mean age at the time of diagnosis was 61.4 years. The prevalence rate was 3.43/100 000 in 2015. In this period, riluzole was prescribed to 53.6% of patients with ALS. Furthermore, 20.3% of patients with ALS underwent tracheostomy. When analysed for age and socioeconomic status, ALS prevalence rate was 10.71 in the aged group (≥60) in 2015 and was lowest in the middle-income group compared with that in the high-income and low-income groups. The estimated mean survival time in this population was 50.0 months, and the 3-year and 5-year mortality rates were 52.1% and 63.7%, respectively.ConclusionsThis study is the first nationwide survey for epidemiological characteristics of ALS in Korea using national data. The use of these data substantially advances the understanding of Korean and Asian ALS epidemiology and its relationship with socioeconomic status, age and sex.