鞘内注射间充质干细胞-神经前体细胞治疗进展性多发性硬化症的疗效：来自 II 期、随机、安慰剂对照临床试验的结果。
Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: results from a phase II, randomized, placebo-controlled clinical trial.
机构信息
Tisch Multiple Sclerosis Research Center of New York, New York, NY, 10019, USA.
Weill Cornell Medicine, Department of Population Health Sciences, New York, NY, USA.
出版信息
Stem Cell Res Ther. 2024 May 23;15(1):151. doi: 10.1186/s13287-024-03765-6.
BACKGROUND
Mesenchymal stem cell-neural progenitors (MSC-NPs) are a bone marrow mesenchymal stem cell (MSC)-derived ex vivo manipulated cell product with therapeutic potential in multiple sclerosis (MS). The objective of this study was to determine efficacy of intrathecal (IT) MSC-NP treatment in patients with progressive MS.
METHODS
The study is a phase II randomized, double-blind, placebo-controlled clinical trial with a compassionate crossover design conducted at a single site. Subjects were stratified according to baseline Expanded Disability Status Scale (EDSS) (3.0-6.5) and disease subtype (secondary or primary progressive MS) and randomized into either treatment or placebo group to receive six IT injections of autologous MSC-NPs or saline every two months. The primary outcome was EDSS Plus, defined by improvement in EDSS, timed 25-foot walk (T25FW) or nine-hole peg test. Secondary outcomes included the individual components of EDSS Plus, the six-minute walk test (6MWT), urodynamics testing, and brain atrophy measurement.
RESULTS
Subjects were randomized into MSC-NP (n = 27) or saline (n = 27) groups. There was no difference in EDSS Plus improvement between the MSC-NP (33%) and saline (37%) groups. Exploratory subgroup analysis demonstrated that in subjects who require assistance for ambulation (EDSS 6.0-6.5) there was a significantly higher percentage of improvement in T25FW and 6MWT in the MSC-NP group (3.7% ± 23.1% and - 9.2% ± 18.2%) compared to the saline group (-54.4% ± 70.5% and - 32.1% ± 30.0%), (p = 0.030 and p = 0.036, respectively). IT-MSC-NP treatment was also associated with improved bladder function and reduced rate of grey matter atrophy on brain MRI. Biomarker analysis demonstrated increased MMP9 and decreased CCL2 levels in the cerebrospinal fluid following treatment.
CONCLUSION
Results from exploratory outcomes suggest that IT-MSC-NP treatment may be associated with a therapeutic response in a subgroup of MS patients.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03355365, registered November 14, 2017, https://clinicaltrials.gov/study/NCT03355365?term=NCT03355365&rank=1 .
背景
骨髓间充质干细胞-神经前体细胞（MSC-NPs）是一种骨髓间充质干细胞（MSC）衍生的体外操纵细胞产物，具有治疗多发性硬化症（MS）的潜力。本研究的目的是确定鞘内（IT）MSC-NP 治疗进展性 MS 患者的疗效。
方法
这是一项在单一地点进行的、具有同情性交叉设计的 II 期随机、双盲、安慰剂对照临床试验。根据基线扩展残疾状况量表（EDSS）（3.0-6.5）和疾病亚型（继发或原发性进展性 MS）对受试者进行分层，并随机分为治疗组或安慰剂组，每两个月接受六次 IT 注射自体 MSC-NP 或生理盐水。主要结局是 EDSS Plus，定义为 EDSS 改善、25 英尺步行计时（T25FW）或 9 孔钉测试的改善。次要结局包括 EDSS Plus 的各个组成部分、6 分钟步行测试（6MWT）、尿动力学测试和脑萎缩测量。
结果
受试者被随机分为 MSC-NP（n=27）或生理盐水（n=27）组。MSC-NP（33%）和生理盐水（37%）组在 EDSS Plus 改善方面无差异。探索性亚组分析表明，在需要辅助行走的受试者（EDSS 6.0-6.5）中，MSC-NP 组的 T25FW 和 6MWT 改善百分比明显更高（3.7%±23.1%和-9.2%±18.2%）与生理盐水组（-54.4%±70.5%和-32.1%±30.0%）相比，（p=0.030 和 p=0.036）。IT-MSC-NP 治疗还与膀胱功能改善和脑 MRI 上灰质萎缩率降低相关。生物标志物分析表明，治疗后脑脊液中 MMP9 水平升高，CCL2 水平降低。
结论
探索性结果表明，IT-MSC-NP 治疗可能与 MS 患者亚组的治疗反应相关。
试验注册
ClinicalTrials.gov NCT03355365，于 2017 年 11 月 14 日注册，https://clinicaltrials.gov/study/NCT03355365？term=NCT03355365&rank=1。
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