Steinberg Gary K, Kondziolka Douglas, Wechsler Lawrence R, Lunsford L Dade, Kim Anthony S, Johnson Jeremiah N, Bates Damien, Poggio Gene, Case Casey, McGrogan Michael, Yankee Ernest W, Schwartz Neil E
1Department of Neurosurgery and Stanford Stroke Center and.
2Department of Neurology and Neurological Sciences and Stanford Stroke Center, Stanford University School of Medicine and Stanford Health Care, Stanford, California.
J Neurosurg. 2018 Nov 23;131(5):1462-1472. doi: 10.3171/2018.5.JNS173147. Print 2019 Nov 1.
The aim of this study was to evaluate the safety and clinical outcomes associated with stereotactic surgical implantation of modified bone marrow-derived mesenchymal stem cells (SB623) in patients with stable chronic ischemic stroke.
This was a 2-year, open-label, single-arm, phase 1/2a study; the selected patients had chronic motor deficits between 6 and 60 months after nonhemorrhagic stroke. SB623 cells were administered to the target sites surrounding the subcortical stroke region using MRI stereotactic image guidance.
A total of 18 patients were treated with SB623 cells. All experienced at least 1 treatment-emergent adverse event (TEAE). No patients withdrew due to adverse events, and there were no dose-limiting toxicities or deaths. The most frequent TEAE was headache related to the surgical procedure (88.9%). Seven patients experienced 9 serious adverse events, which resolved without sequelae. In 16 patients who completed 24 months of treatment, statistically significant improvements from baseline (mean) at 24 months were reported for the European Stroke Scale (ESS) score, 5.7 (95% CI 1.4-10.1, p < 0.05); National Institutes of Health Stroke Scale (NIHSS) score, -2.1 (95% CI -3.3 to -1.0, p < 0.01), Fugl-Meyer (F-M) total score, 19.4 (95% CI 9.9-29.0, p < 0.01); and F-M motor scale score, 10.4 (95% CI 4.0-16.7, p < 0.01). Measures of efficacy reached plateau by 12 months with no decline thereafter. There were no statistically significant changes in the modified Rankin Scale score. The size of transient lesions detected by T2-weighted FLAIR imaging in the ipsilateral cortex at weeks 1-2 postimplantation significantly correlated with improvement in ESS (0.619, p < 0.05) and NIHSS (-0.735, p < 0.01) scores at 24 months.
In this completed 2-year phase 1/2a study, implantation of SB623 cells in patients with stable chronic stroke was safe and was accompanied by improvements in clinical outcomes.Clinical trial registration no.: NCT01287936 (clinicaltrials.gov).
本研究旨在评估改良的骨髓间充质干细胞（SB623）立体定向手术植入稳定型慢性缺血性脑卒中患者后的安全性及临床疗效。
这是一项为期2年的开放标签、单臂1/2a期研究；入选患者在非出血性脑卒中后6至60个月存在慢性运动功能缺损。使用MRI立体定向图像引导将SB623细胞注入皮质下卒中区域周围的靶点。
共有18例患者接受了SB623细胞治疗。所有患者均经历了至少1次治疗中出现的不良事件（TEAE）。无患者因不良事件退出研究，也未出现剂量限制性毒性反应或死亡。最常见的TEAE是与手术相关的头痛（88.9%）。7例患者发生了9次严重不良事件，均痊愈且无后遗症。在完成24个月治疗的16例患者中，欧洲卒中量表（ESS）评分在第24个月时较基线（均值）有统计学意义的显著改善，为5.7（95%CI 1.4 - 10.1，p < 0.05）；美国国立卫生研究院卒中量表（NIHSS）评分改善了 -2.1（95%CI -3.3至 -1.0，p < 0.01），Fugl-Meyer（F-M）总分改善了19.4（95%CI 9.9 - 29.0，p < 0.01）；F-M运动量表评分改善了10.4（95%CI 4.0 - 16.7，p < 0.01）。疗效指标在12个月时达到平台期，此后未下降。改良Rankin量表评分无统计学意义的变化。植入后1 - 2周在同侧皮质通过T2加权液体衰减反转恢复序列（FLAIR）成像检测到的短暂性病变大小与第24个月时ESS评分的改善（0.619，p < 0.05）和NIHSS评分的改善（-0.735，p < 0.01）显著相关。
在这项完成的为期2年的1/2a期研究中，SB623细胞植入稳定型慢性卒中患者体内是安全的，并伴有临床疗效的改善。临床试验注册号：NCT01287936（clinicaltrials.gov）。
