Kinetics of serum NFL and GFAP and changes in cognitive functions, in MS patients treated with repeated administrations of autologous mesenchymal stem cells (MSC-NG01)

IF 2.9 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology Pub Date : 2025-04-08 DOI:10.1016/j.jneuroim.2025.578613

Panayiota Petrou, Ibrahim Kassis, Yarden Levi, Nour Yaghmour, Tehila Epstein, Ariel Ginzberg, Dimitrios Karussis

{"title":"Kinetics of serum NFL and GFAP and changes in cognitive functions, in MS patients treated with repeated administrations of autologous mesenchymal stem cells (MSC-NG01)","authors":"Panayiota Petrou, Ibrahim Kassis, Yarden Levi, Nour Yaghmour, Tehila Epstein, Ariel Ginzberg, Dimitrios Karussis","doi":"10.1016/j.jneuroim.2025.578613","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Intrathecal injection (IT) of autologous mesenchymal stem cells (MSC) showed robust beneficial effects a previous randomized study from our center, in patients with progressive multiple sclerosis (MS) (<span><span>NCT02166021</span><svg><path></path></svg></span>). We evaluated here the effect of repeated MSC-NG01 transplantations on serum biomarkers of neuroinflammation and neurodegeneration, namely, neurofilaments light chains (NFL) and glial fibrillary acidic protein (GFAP), in an open-label extension trial.</div></div><div><h3>Methods</h3><div>23 patients with progressive types of MS, who participated in the <span><span>NCT02166021</span><svg><path></path></svg></span>-trial, were included. Patients were treated with 2–3 intrathecal injections of MSC-NG01 and followed up for a period of >12 months. Safety/tolerability and various efficacy measurements, including EDSS/FS, timed 25-ft (T25FW) walking, cognitive functions, and serum levels of the biomarkers NFL and GFAP, were assessed.</div></div><div><h3>Results</h3><div>Serum levels of NFL and GFAP showed a gradual and consistent reduction after the intrathecal treatments with MSC-NG01, in multiple measurements. The mean NFL reduction at last observation after one year was 33.2 % (<em>p</em> < 0.001, Wilcoxon-paired test). Serum levels of GFAP were reduced in all tested patients (<em>p</em> < 0.0004, Wilcoxon-paired test). A significant improvement was observed in T25-FW and in the sum of all functional systems (FS) at the final visit of 12 months. SDMT cognitive test was also improved by a mean of >3 degrees (<em>p</em> = 0.0008).</div></div><div><h3>Conclusion</h3><div>Treatment of progressive MS patients with IT injections of autologous MSC-NG01 induced a reduction in both NFL and GFAP biomarkers levels, paralleled by beneficial effects on cognition, neurological functional tests and quality of life. These data indicate significant effects of MSC-transplantation on neurodegeneration and neuroinflammation.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"403 ","pages":"Article 578613"},"PeriodicalIF":2.9000,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neuroimmunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0165572825000943","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Intrathecal injection (IT) of autologous mesenchymal stem cells (MSC) showed robust beneficial effects a previous randomized study from our center, in patients with progressive multiple sclerosis (MS) (NCT02166021). We evaluated here the effect of repeated MSC-NG01 transplantations on serum biomarkers of neuroinflammation and neurodegeneration, namely, neurofilaments light chains (NFL) and glial fibrillary acidic protein (GFAP), in an open-label extension trial.

Methods

23 patients with progressive types of MS, who participated in the NCT02166021-trial, were included. Patients were treated with 2–3 intrathecal injections of MSC-NG01 and followed up for a period of >12 months. Safety/tolerability and various efficacy measurements, including EDSS/FS, timed 25-ft (T25FW) walking, cognitive functions, and serum levels of the biomarkers NFL and GFAP, were assessed.

Results

Serum levels of NFL and GFAP showed a gradual and consistent reduction after the intrathecal treatments with MSC-NG01, in multiple measurements. The mean NFL reduction at last observation after one year was 33.2 % (p < 0.001, Wilcoxon-paired test). Serum levels of GFAP were reduced in all tested patients (p < 0.0004, Wilcoxon-paired test). A significant improvement was observed in T25-FW and in the sum of all functional systems (FS) at the final visit of 12 months. SDMT cognitive test was also improved by a mean of >3 degrees (p = 0.0008).

Conclusion

Treatment of progressive MS patients with IT injections of autologous MSC-NG01 induced a reduction in both NFL and GFAP biomarkers levels, paralleled by beneficial effects on cognition, neurological functional tests and quality of life. These data indicate significant effects of MSC-transplantation on neurodegeneration and neuroinflammation.

查看原文本刊更多论文

背景鞘内注射（IT）自体间充质干细胞（MSC）对进行性多发性硬化症（MS）（NCT02166021）患者有显著的疗效。我们在此评估了重复移植间充质干细胞-NG01对神经炎症和神经变性血清生物标志物，即神经丝蛋白轻链（NFL）和胶质纤维酸性蛋白（GFAP）的影响。患者接受了 2-3 次间叶干细胞-NG01 鞘内注射治疗，并随访了 12 个月。结果MSC-NG01鞘内注射治疗后，患者血清中的NFL和GFAP水平在多项测量中均显示出逐渐且持续的下降。在一年后的最后一次观察中，NFL 的平均下降率为 33.2%（p < 0.001，Wilcoxon-pired 检验）。所有接受测试的患者血清中的 GFAP 水平都有所下降（p < 0.0004，Wilcoxon-pired 检验）。在 12 个月的最终检查中，T25-FW 和所有功能系统（FS）的总和均有明显改善。结论对进展期多发性硬化症患者进行 IT 注射自体间充质干细胞-NG01 治疗，可降低 NFL 和 GFAP 生物标志物水平，同时对认知、神经功能测试和生活质量产生有益影响。这些数据表明间充质干细胞移植对神经退行性变和神经炎症有明显的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of neuroimmunology 医学-免疫学

CiteScore

6.10

自引率

3.00%

发文量

154

审稿时长

37 days

期刊介绍： The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication.