Lee Jiwon, Park Sang Eon, Kim Mira, Kim Hyeongseop, Kwon Jeong-Yi, Jeon Hong Bae, Chang Jong Wook, Lee Jeehun
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Cell and Gene Therapy Research Institute, ENCell Co. Ltd., Seoul, Korea.
J Clin Neurol. 2025 Jan;21(1):40-52. doi: 10.3988/jcn.2024.0299.
This study was an open-label, dose-escalation, phase 1 clinical trial to determine the safety and dose of EN001 for patients with Duchenne muscular dystrophy (DMD). EN001, developed by ENCell, are allogeneic early-passage Wharton's jelly-derived mesenchymal stem cells that originate at the umbilical cord, with preclinical studies demonstrating their high therapeutic efficacy for DMD.
This phase 1 clinical trial explored the safety and tolerability of EN001 as a potential treatment option for patients with DMD. Six pediatric participants with DMD were divided into two subgroups of equal size: low-dose EN001 (5.0×10⁵ cells/kg) and high-dose EN001 (2.5×10⁶ cells/kg). All participants were monitored for 12 weeks after EN001 administration to assess its safety. Dose-limiting toxicity (DLT) was evaluated across 2 weeks post administration. Exploratory efficacy was evaluated by measuring serum creatine kinase levels, and functional evaluations-including spirometry, myometry, the North Star Ambulatory Assessment, and the 6-minute walk test-were conducted at week 12 and compared with the baseline values.
No participants experienced serious adverse events related to EN001 injection during the 12-week follow-up period. Mild adverse events included injection-related local erythema, edema, parosmia, and headache, but DLT was not observed. Functional evaluations at week 12 revealed no significant changes from baseline.
These results demonstrated that EN001 are safe and well tolerated for patients with DMD, and did not cause serious adverse events. The efficacy of EN001 could be confirmed through larger-scale future studies that incorporate repeated dosing and have a randomized controlled trial design.
本研究是一项开放标签、剂量递增的1期临床试验，旨在确定EN001用于杜氏肌营养不良症（DMD）患者的安全性和剂量。EN001由ENCell公司研发，是源自脐带的同种异体早期传代华通氏胶间充质干细胞，临床前研究表明其对DMD具有较高的治疗效果。
这项1期临床试验探讨了EN001作为DMD患者潜在治疗选择的安全性和耐受性。6名患有DMD的儿科参与者被平均分为两个亚组：低剂量EN001（5.0×10⁵个细胞/千克）和高剂量EN001（2.5×10⁶个细胞/千克）。所有参与者在接受EN001治疗后接受12周的监测以评估其安全性。给药后2周内评估剂量限制性毒性（DLT）。通过测量血清肌酸激酶水平评估探索性疗效，并在第12周进行功能评估，包括肺活量测定、肌力测定、北极星动态评估和6分钟步行试验，并与基线值进行比较。
在12周的随访期内，没有参与者经历与EN001注射相关的严重不良事件。轻度不良事件包括注射相关的局部红斑、水肿、嗅觉异常和头痛，但未观察到DLT。第12周的功能评估显示与基线相比无显著变化。
这些结果表明，EN001对DMD患者是安全的且耐受性良好，并且不会引起严重不良事件。EN001的疗效可以通过未来纳入重复给药并采用随机对照试验设计的更大规模研究来证实。
