Department of Neurology, Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Mult Scler. 2023 Jan;29(1):92-106. doi: 10.1177/13524585221122156. Epub 2022 Sep 14.
Autologous mesenchymal stem cell neurotrophic factor-secreting cells (NurOwn) have the potential to modify underlying disease mechanisms in progressive multiple sclerosis (PMS).
This open-label phase II study was conducted to evaluate safety/efficacy of three intrathecal cell treatments.
Eighteen participants with non-relapsing PMS were treated. The primary endpoint was safety. Secondary endpoints included: cerebrospinal fluid (CSF) biomarkers; timed 25-foot walk speed, nine-hole peg test (9-HPT), low-contrast letter acuity, symbol digit modalities test, and 12-item multiple sclerosis (MS) walking scale. Seventeen participants received all treatments.
No deaths/adverse events related to worsening of MS, clinical/magnetic resonance imaging (MRI) evidence of disease activation, and clinically significant changes in safety lab results were reported. Two participants developed symptoms of low back and leg pain, consistent with a diagnosis of arachnoiditis, occurring in one of three intrathecal treatments in both participants. Nineteen percent of treated participants achieved pre-specified ⩾ 25% improvements in timed 25-foot walk speed/nine-HPT at 28 weeks compared to baseline, along with consistent efficacy signals for pre-specified response criteria across other secondary efficacy outcomes. CSF neuroprotective factors increased, and inflammatory biomarkers decreased after treatment, consistent with the proposed mechanism of action.
Based on these encouraging preliminary findings, further confirmation in a randomized study is warranted.
自体间充质干细胞神经营养因子分泌细胞（NurOwn）有可能改变进行性多发性硬化症（PMS）的潜在疾病机制。
本开放性 2 期研究旨在评估三种鞘内细胞治疗的安全性/疗效。
18 名非复发 PMS 参与者接受了治疗。主要终点是安全性。次要终点包括：脑脊液（CSF）生物标志物；定时 25 英尺步行速度、九孔钉测试（9-HPT）、低对比度字母视力、符号数字模式测试和 12 项多发性硬化症（MS）步行量表。17 名参与者接受了所有治疗。
未报告与 MS 恶化、临床/磁共振成像（MRI）疾病活动证据以及安全实验室结果的临床显著变化相关的死亡/不良事件。两名参与者出现了腰痛和腿部疼痛的症状，与蛛网膜炎的诊断一致，这两种症状都发生在两名参与者的三种鞘内治疗中的一种中。与基线相比，19%的治疗参与者在 28 周时达到了预定的定时 25 英尺步行速度/9-HPT ⩾25%的改善，并且在其他次要疗效终点的预定反应标准中也有一致的疗效信号。CSF 神经保护因子增加，炎症生物标志物减少，这与预期的作用机制一致。
基于这些令人鼓舞的初步发现，需要在随机研究中进一步证实。
