Department of Neurosurgery, Emory University, Atlanta, Georgia 30322, USA.
Neurosurgery. 2012 Aug;71(2):405-16; discussion 416. doi: 10.1227/NEU.0b013e31825ca05f.
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.
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.
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.
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.
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.
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）。
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。
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。
12 名患者已接受移植。术中出现 1 次短暂体感诱发电位抑制。术后即刻，有 1 例尿潴留需要重新插入 Foley 导管。出院时，均无明确的运动功能减退。2 例患者因脑脊液漏或筋膜上伤口裂开（各 1 例）需要再次入院和再次手术。2 例死亡发生在术后 8 个月和 13 个月；均与手术移植无关。
我们在 12 名患者中的经验支持单侧和双侧脊柱内腰椎微注射的程序安全性。计划通过在 ALS 患者中进行颈椎和颈椎+腰椎联合微注射来完成这项 I 期安全性试验。
