Manager / Dr. ENCell Co. Ltd. Seoul, Seoul-t'ukpyolsi, Republic of Korea
Abstract: Charcot-Marie-Tooth disease type 1A (CMT1A) is an inherited peripheral neuropathy resulting from a duplication mutation in the PMP22 gene and is one of the most prevalent orphan diseases. Symptoms include sensory loss, muscle atrophy, and gait disturbances, affecting an estimated 1.5 million people globally, with no cure available. This study is a Phase 1 clinical trial to assess the safety, tolerability, and preliminary efficacy of Wharton's jelly-derived mesenchymal stem cells (EN001) in patients with CMT1A. A total of nine patients with CMT1A participated in this study. The participants received EN001 intravenously, with three participants assigned to the low-dose group (5 × 10^5 cells/kg) and six to the high-dose group (2.5 × 10^6 cells/kg). The safety and tolerability assessments were conducted 16 weeks post-administration. Exploratory efficacies were evaluated during a 48-week follow-up period. Exploratory efficacy endpoints included CMTNSv2, CMTNSv2-R, CMTES, CMTES-R, ONLS, 10 MWT, NCS, and MRI. There were a total of four adverse events, but mild (Grade 1) and transient during 16 weeks. Those events were determined to be unrelated or unlikely to the investigational products (EN001). There were no additional adverse events related to EN001 from Week 16 to Week 48. Significant improvements were found in CMTNSv2, CMTNSv2-R, CMTES, and CMTES-R in the high-dose groups at Week 16. The disease severity classification of CMTNSv2 was changed from moderate to mild in the high-dose group. All subjects maintained improvements at Week 48, in particular, CMTES and CMTES-R in the high-dose groups showed significant improvements in disease severity classifications from moderate to mild. FDS scores decreased significantly at Week 48 compared to the baseline. Specifically, two participants in the high-dose group scored zero, which is normal, at Week 16 and remained until Week 48. Intravenous administration of EN001 in patients with CMT1A confirmed safety and tolerability. Significant improvements in motor function, particularly in the high-dose group, were observed for 48 weeks after administration. Long-term follow-up is planned for five years. These results suggest that EN001 could be an effective treatment option for CMT1A.
Funding Source: This research was supported by the Ministry of Science and ICT, and the Ministry of Health and Welfare (RS-2023-00215098, HX23C1756); the National Research Foundation (2022M3E5E9016662); and the Samsung Medical Center (SMO1240041)
