Self-renewal capacity and potential to differentiate into almost any cell type of the human body makes pluripotent stem cells a valuable starting material for manufacturing of clinical grade cell therapies. Neurodegenerative diseases are characterized by gradual loss of structure or function of neurons, often leading to neuronal death. This results in gradual decline of cognitive, motor, and physiological functions due to the degeneration of the central nervous systems. Over the past two decades, comprehensive preclinical efficacy (proof-of-concept) and safety studies have led to the initiation of First-in-Human phase I-II clinical trials for a range of neurodegenerative diseases. In this review, we explore the fundamentals and challenges of neural-cell therapies derived from pluripotent stem cells for treating neurodegenerative diseases. Additionally, we highlight key preclinical investigations that paved the way for regulatory approvals of these trials. Furthermore, we provide an overview on progress and status of clinical trials done so far in treating neurodegenerative diseases such as spinal cord injury (SCI), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), as well as advances in retina diseases such as Stargardt disease (a.k.a fundus flavimaculatus), retinitis pigmentosa (RP) and age-related macular degeneration (AMD). These trials will pave the way for the development of new cell-based therapies targeting additional neurological conditions, including Alzheimer’s disease and epilepsy.

中文翻译：

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多能干细胞衍生细胞疗法治疗神经退行性疾病的临床观点


自我更新能力和分化为人体几乎任何细胞类型的潜力使多能干细胞成为制造临床级细胞疗法的宝贵起始材料。神经退行性疾病的特征是神经元结构或功能逐渐丧失，通常会导致神经元死亡。由于中枢神经系统的退化，这导致认知、运动和生理功能逐渐下降。在过去的二十年里，全面的临床前疗效（概念验证）和安全性研究已经启动了针对一系列神经退行性疾病的首次人体 I-II 期临床试验。在这篇综述中，我们探讨了源自多能干细胞的神经细胞疗法治疗神经退行性疾病的基本原理和挑战。此外，我们还重点介绍了为这些试验的监管批准铺平道路的关键临床前研究。此外，我们概述了迄今为止在治疗神经退行性疾病（如脊髓损伤 （SCI）、帕金森病 （PD） 和肌萎缩侧索硬化症 （ALS））以及视网膜疾病的进展，如 Stargardt 病（又名黄斑底）、视网膜色素变性 （RP） 和年龄相关性黄斑变性 （AMD）。这些试验将为开发针对其他神经系统疾病（包括阿尔茨海默病和癫痫）的新型细胞疗法铺平道路。