News
Article
Preclinical Study Suggests Stem Cell Therapy EN001 and Insulin May Improve Symptoms of Charcot-Marie-Tooth Disease Type 1A
Key Takeaways
- EN001 and insulin improved muscle strength, endurance, and remyelination in CMT1A preclinical models, with combination therapy showing enhanced benefits.
- Schwann cell proliferation and nerve regeneration were significantly promoted by both treatments, with a reduced insulin dose in combination therapy.
Researchers reported that both EN001 and insulin improved muscle strength and nerve function in models of Charcot-Marie-Tooth disease type 1A, with combined treatment showing enhanced effects.
Jong Wook Chang, PhD
(Credit: Sungkyunkwan University)
Investigators recently reported that both EN001 (ENCell), a Wharton’s jelly-derived investigational mesenchymal stem cell therapy, and insulin improved skeletal muscle strength, endurance, and remyelination in preclinical models of Charcot-Marie-Tooth disease type 1A (CMT1A). Presented at the 2025 Peripheral Nerve Society (PNS) Annual Meeting, held May 17-20, in Edinburgh, Scotland, results suggested that the combination of both treatments yielded greater therapeutic benefits.1
In this study, researchers assessed the therapeutic potential of EN001 and insulin in models of CMT1A, including S16 and patient-derived iPSC Schwann cells. All told, findings revealed that both agents significantly promoted Schwann cell proliferation and led to improved muscle performance and nerve regeneration in the treated animals. Notably, investigators observed an improvement in benefit with the combination therapy, which also allowed for a reduced insulin dose.
Conducted by senior author Jong Wook Chang, PhD, a professor in the Samsung Advanced Institute for Health Sciences & Technology at Sungkyunkwan University, in Korea, CMT1A in vitro models were treated with EN001 or insulin. At the conclusion of the study, both treatments significantly increased Schwann cell proliferation in a dose-dependent manner. In vivo, administration of either EN001 or insulin to CMT1A mouse models resulted in improved skeletal muscle strength and endurance.
A histological analysis revealed remyelination and increased expression of myelin protein zero (MPZ) in the sciatic nerves. Authors noted that the combination of EN001 and insulin amplified these therapeutic effects observed in the preclinical models. Notably, researchers reported that EN001 exposed to insulin entered a highly proliferative and secretory state, potentially further enhancing the observed benefits. According to the investigators, this study was the first to report insulin as a potential therapeutic option for CMT1A.
In March 2025, ENCell announced that the FDA granted EN001 orphan drug designation for the treatment of CMT. EN001 is a mesenchymal stem cell therapy created through the company’s proprietary ENCT (ENCell Technology) platform, which is designed to extend cell lifespan and boost the release of therapeutic molecules. After administration, EN001 acts on damaged nerves by supporting the release of regenerative factors and aiding in remyelination.
In October 2024, the company announced findings from a phase 1 trial assessing the safety and preliminary efficacy of repeated low-dose EN001 in patients with CMT1A. In the trial, 3 participants received 2 doses of the therapy, with dose-limiting toxicity evaluated 8 weeks after treatment. No dose-limiting toxicities, serious adverse events, or injection-related reactions were reported by the investigators.
Following these results, ENCell launched a phase 1b trial with a higher dose cohort in December 2024, with completion targeted for 2025. The company also noted that EN001 is also being studied for additional indications, including Duchenne muscular dystrophy and sarcopenia.
Click here for more PNS 2025 coverage.
