Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan.
Cell Transplant. 2023 Jan-Dec;32:9636897231214370. doi: 10.1177/09636897231214370.
Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons. Multilineage-differentiating stress-enduring (Muse) cells are unique endogenous stem cells that show therapeutic effects on motor function in ALS mouse models. We conducted a single-center open phase II clinical trial to evaluate the safety and clinical effects of repeated intravenous injections of an allogenic Muse cell-based product, CL2020, in patients with ALS. Five patients with ALS received CL2020 intravenously once a month for a total of six doses. The primary endpoints were safety and tolerability, and the secondary endpoint was the rate of change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score. In addition, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), sphingosine-1-phosphate (S1P), cerebrospinal fluid chitotriosidase-1 (CHIT-1), and neurofilament light chain (NfL) levels were evaluated. The CL2020 treatment was highly tolerated without serious side effects. The ALSFRS-R score change trended upward at 12 months post-CL2020 treatment compared with that at 3 months pre-administration, but the difference was not statistically significant. Among five patients diagnosed with ALS, three exhibited a decrease in the rate of ALSFRS-R score change, one demonstrated an increase, and another showed no change. In addition, the patients' serum IL-6 and TNF-α levels and cerebrospinal fluid CHIT-1 and NfL levels increased for up to 6 months post-treatment; however, their serum S1P levels continuously decreased over 12 months. These findings indicate a favorable safety profile of CL2020 therapy. In the near future, a double-blind study of a larger number of ALS patients should be conducted to confirm the efficacy of ALS treatment with CL2020.
肌萎缩侧索硬化症（ALS）的特征是运动神经元进行性丧失。多谱系分化应激耐受（Muse）细胞是独特的内源性干细胞，在 ALS 小鼠模型中显示出对运动功能的治疗作用。我们进行了一项单中心开放的 II 期临床试验，以评估重复静脉注射同种异体 Muse 细胞产品 CL2020 在 ALS 患者中的安全性和临床效果。5 名 ALS 患者每月静脉注射一次 CL2020，共 6 剂。主要终点是安全性和耐受性，次要终点是修订后的肌萎缩侧索硬化功能评定量表（ALSFRS-R）评分的变化率。此外，还评估了血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、鞘氨醇-1-磷酸（S1P）、脑脊液几丁质酶-1（CHIT-1）和神经丝轻链（NfL）水平。CL2020 治疗具有高度耐受性，无严重副作用。与治疗前 3 个月相比，CL2020 治疗后 12 个月的 ALSFRS-R 评分变化呈上升趋势，但差异无统计学意义。在 5 名被诊断为 ALS 的患者中，3 名患者的 ALSFRS-R 评分变化率下降，1 名患者增加，另 1 名患者无变化。此外，患者的血清 IL-6 和 TNF-α水平以及脑脊液 CHIT-1 和 NfL 水平在治疗后长达 6 个月内升高；然而，他们的血清 S1P 水平在 12 个月内持续下降。这些发现表明 CL2020 治疗具有良好的安全性。在不久的将来，应该进行一项更大规模的 ALS 患者的双盲研究，以确认 CL2020 治疗 ALS 的疗效。
