IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1, San Giovanni Rotondo, 71013 Foggia, Italy.
Multiple Sclerosis Centre (MSC), Department of Neurology, Neurocentre of Southern Switzerland, EOC, 6900 Lugano, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), 6900 Lugano, Switzerland.
Cell Stem Cell. 2023 Dec 7;30(12):1597-1609.e8. doi: 10.1016/j.stem.2023.11.001. Epub 2023 Nov 27.
We report the analysis of 1 year of data from the first cohort of 15 patients enrolled in an open-label, first-in-human, dose-escalation phase I study (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive multiple sclerosis. Participants were treated with hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed. All participants displayed stability of clinical and laboratory outcomes, as well as lesion load and brain activity (MRI), compared with the study entry. Longitudinal metabolomics and lipidomics of biological fluids identified time- and dose-dependent responses with increased levels of acyl-carnitines and fatty acids in the cerebrospinal fluid (CSF). The absence of AEs and the stability of functional and structural outcomes are reassuring and represent a milestone for the safe translation of stem cells into regenerative medicines.
我们报告了首个人体开放标签、剂量递增 I 期研究（ClinicalTrials.gov：NCT03282760，EudraCT2015-004855-37）中前 15 名患者队列 1 年数据的分析，该研究旨在确定同种异体人神经干细胞/祖细胞（hNSCs）移植治疗继发进展性多发性硬化症的可行性、安全性和耐受性。参与者接受了通过脑室内注射给予的 hNSCs 联合免疫抑制方案的治疗。未观察到与治疗相关的死亡或严重不良事件（AE）。与研究入组时相比，所有参与者的临床和实验室结果、病变负荷和脑活动（MRI）均保持稳定。生物体液的纵向代谢组学和脂质组学分析鉴定出时间和剂量依赖性反应，脑脊液（CSF）中的酰基辅酶 A 和脂肪酸水平升高。没有发生 AE，并且功能和结构结果保持稳定，令人感到放心，这代表了将干细胞安全转化为再生医学的一个里程碑。
