Oh Ki-Wook, Moon Chanil, Kim Hyun Young, Oh Sung-Il, Park Jinseok, Lee Jun Ho, Chang In Young, Kim Kyung Suk, Kim Seung Hyun
Department of Neurology, College of Medicine and Cell Therapy Center for Neurologic Disorders, Hanyang University Hospital, Seoul, Republic of Korea; Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; Bioengineering Institute, Corestem Inc., Seoul, Republic of Korea.
Department of Neurology, College of Medicine and Cell Therapy Center for Neurologic Disorders, Hanyang University Hospital, Seoul, Republic of Korea; Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea; Bioengineering Institute, Corestem Inc., Seoul, Republic of Korea
Stem Cells Transl Med. 2015 Jun;4(6):590-7. doi: 10.5966/sctm.2014-0212. Epub 2015 May 1.
Stem cell therapy is an emerging alternative therapeutic or disease-modifying strategy for amyotrophic lateral sclerosis (ALS). The aim of this open-label phase I clinical trial was to evaluate the safety of two repeated intrathecal injections of autologous bone marrow (BM)-derived mesenchymal stromal cells (MSCs) in ALS patients. Eight patients with definite or probable ALS were enrolled. After a 3-month lead-in period, autologous MSCs were isolated two times from the BM at an interval of 26 days and were then expanded in vitro for 28 days and suspended in autologous cerebrospinal fluid. Of the 8 patients, 7 received 2 intrathecal injections of autologous MSCs (1 × 10(6) cells per kg) 26 days apart. Clinical or laboratory measurements were recorded to evaluate the safety 12 months after the first MSC injection. The ALS Functional Rating Scale-Revised (ALSFRS-R), the Appel ALS score, and forced vital capacity were used to evaluate the patients' disease status. One patient died before treatment and was withdrawn from the study. With the exception of that patient, no serious adverse events were observed during the 12-month follow-up period. Most of the adverse events were self-limited or subsided after supportive treatment within 4 days. Decline in the ALSFRS-R score was not accelerated during the 6-month follow-up period. Two repeated intrathecal injections of autologous MSCs were safe and feasible throughout the duration of the 12-month follow-up period.
Stem cell therapy is an emerging alternative therapeutic or disease-modifying strategy for amyotrophic lateral sclerosis (ALS). To the authors' best knowledge, there are no clinical trials to evaluate the safety of repeated intrathecal injections of autologous bone marrow mesenchymal stromal cells in ALS. After the clinical trial (phase I/II) was conducted, the stem cell (HYNR-CS, NEURONATA-R) was included in the revision of the regulations on orphan drug designation (number 160; December 31, 2013) and approved as a New Drug Application (Department of Cell and Gene Therapy 233; July 30, 2014) by the Korean Food and Drug Administration. The phase II trial is expected to be reported later.
干细胞疗法是一种用于肌萎缩侧索硬化症（ALS）的新兴替代治疗或疾病改善策略。这项开放标签的I期临床试验旨在评估对ALS患者进行两次重复鞘内注射自体骨髓（BM）来源的间充质基质细胞（MSC）的安全性。招募了8名明确或可能患有ALS的患者。在为期3个月的导入期后，从骨髓中两次分离自体MSC，间隔26天，然后在体外扩增28天，并悬浮于自体脑脊液中。8名患者中，7名接受了两次间隔26天的鞘内注射自体MSC（每千克1×10⁶个细胞）。在首次注射MSC后12个月记录临床或实验室测量结果以评估安全性。使用修订的ALS功能评定量表（ALSFRS-R）、阿佩尔ALS评分和用力肺活量来评估患者的疾病状态。1名患者在治疗前死亡并退出研究。除该患者外，在12个月的随访期内未观察到严重不良事件。大多数不良事件为自限性或在4天内支持治疗后消退。在6个月的随访期内，ALSFRS-R评分未加速下降。在12个月的随访期内，两次重复鞘内注射自体MSC在整个过程中都是安全可行的。
干细胞疗法是一种用于肌萎缩侧索硬化症（ALS）的新兴替代治疗或疾病改善策略。据作者所知，尚无临床试验评估在ALS中重复鞘内注射自体骨髓间充质基质细胞的安全性。在进行该临床试验（I/II期）后，该干细胞（HYNR-CS，NEURONATA-R）被纳入孤儿药指定法规修订（第160号；2013年12月31日），并被韩国食品药品管理局批准作为新药申请（细胞与基因治疗部233号；2014年7月30日）。预计II期试验结果将在以后报告。
