Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis

IF 19.8 1区医学 Q1 CELL & TISSUE ENGINEERING Cell stem cell Pub Date : 2023-11-27 DOI:10.1016/j.stem.2023.11.001

Maurizio A. Leone, Maurizio Gelati, Daniela C. Profico, Claudio Gobbi, Emanuele Pravatà, Massimiliano Copetti, Carlo Conti, Lucrezia Abate, Luigi Amoruso, Francesco Apollo, Rosario F. Balzano, Ilaria Bicchi, Massimo Carella, Alessandro Ciampini, Carlo Colosimo, Paola Crociani, Giada D’Aloisio, Pietro Di Viesti, Daniela Ferrari, Danilo Fogli, Angelo L. Vescovi

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Abstract

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.

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异体神经干细胞在进行性多发性硬化症患者脑室内移植的I期临床试验

我们报告了一项开放标签、首次在人体进行、剂量递增的I期研究(ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37)的1年数据分析，以确定异体人神经干细胞/祖细胞(hNSCs)移植治疗继发性进行性多发性硬化症的可行性、安全性和耐受性。参与者通过脑室内注射hNSCs并结合免疫抑制方案进行治疗。未观察到治疗相关死亡和严重不良事件(ae)。与研究开始时相比，所有参与者都表现出临床和实验室结果的稳定性，以及病变负荷和脑活动(MRI)。生物体液的纵向代谢组学和脂质组学确定了脑脊液(CSF)中酰基肉碱和脂肪酸水平增加的时间和剂量依赖性反应。ae的缺失以及功能和结构结果的稳定性令人放心，并且代表了干细胞安全转化为再生药物的里程碑。

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来源期刊

Cell stem cell 生物-细胞生物学

CiteScore

37.10

自引率

2.50%

发文量

151

审稿时长

42 days

期刊介绍： Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.