脊髓内干细胞移植治疗肌萎缩侧索硬化症：I 期安全性试验、技术说明及腰椎安全性结果。

Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: a phase I safety trial, technical note, and lumbar safety outcomes.

机构信息

Department of Neurosurgery, Emory University, Atlanta, Georgia 30322, USA.

出版信息

Neurosurgery. 2012 Aug;71(2):405-16; discussion 416. doi: 10.1227/NEU.0b013e31825ca05f.

DOI:10.1227/NEU.0b013e31825ca05f

PMID:22565043

Abstract

BACKGROUND

No United States-based clinical trials have attempted delivery of biological therapies directly to the spinal cord for treatment of amyotrophic lateral sclerosis (ALS) because of the lack of a meaningful US Food and Drug Administration-authorized cell candidate and a validated delivery approach.

OBJECTIVE

To assess safety of delivery of a neural stem cell-based treatment into the upper lumbar segments of the ALS spinal cord in the first US Food and Drug Administration-authorized phase I trial.

METHODS

Each microinjection series comprised 5 injections (10 μL/injection) separated by 4 mm. Each injection deposited 100,000 neural stem cells derived from a fetal spinal cord. Twelve patients were treated with either unilateral or bilateral injections. Group A, nonambulatory patients, underwent unilateral (n = 3) or bilateral (n = 3) lumbar microinjections. Groups B and C were ambulatory (n = 3 each) and, respectively, received unilateral or bilateral injections. Patients are followed clinically and radiologically to assess potential toxicity of the procedure.

RESULTS

Twelve patients have received a transplant. There was one instance of transient intraoperative somatosensory-evoked potentials depression. In the immediate postoperative period, there was 1 episode of urinary retention requiring Foley catheter reinsertion. By discharge, none had a documented motor function decrement. Two patients required readmission and reoperation for cerebrospinal fluid leak or suprafascial wound dehiscence (n = 1 each). Two deaths occurred at 8 and 13 months postsurgery; neither was related to the surgical transplant.

CONCLUSION

Our experience in 12 patients supports the procedural safety of unilateral and bilateral intraspinal lumbar microinjection. Completion of this phase I safety trial is planned by proceeding to cervical and combined cervical + lumbar microinjections in ALS patients.

摘要

背景

由于缺乏有意义的美国食品和药物管理局批准的细胞候选物和经过验证的递药方法，因此，没有任何一项基于美国的临床试验尝试过将生物疗法直接递送到脊髓来治疗肌萎缩侧索硬化症（ALS）。

目的

评估将基于神经干细胞的治疗方法递送至 ALS 脊髓上腰椎段的安全性，这是首次经美国食品和药物管理局批准的 I 期试验。

方法

每次微注射系列包括 5 次注射（每次 10 μL），间隔 4mm。每次注射都沉积了 10 万个源自胎儿脊髓的神经干细胞。12 名患者接受单侧或双侧注射治疗。A 组为非运动患者，行单侧（n=3）或双侧（n=3）腰椎微注射。B 组和 C 组为运动患者（n=3 例），分别接受单侧或双侧注射。通过临床和影像学检查评估该程序的潜在毒性。