Advancing human neural progenitor cells (hNPCs) to FDA IND approval

推动人类神经祖细胞 (hNPC) 获得 FDA IND 批准

• 批准号: 10642228
• 负责人: MARK H. TUSZYNSKI
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10642228
• 关键词: Axon; Cell Line; Cells; Cervical spinal cord structure; Chronic; Clinical Trials; Contusions; Funding; Goals; Graft Survival; Human; Human Cell Line; Injury; Intervention; Lesion; Macaca mulatta; Natural regeneration; Primates; Readiness; Recovery of Function; Rehabilitation therapy; Rodent; Services; Site; Spinal; Spinal Cord; Spinal cord injury; Synapses; United States Food and Drug Administration; Vertebral column; Veterans; Work; clinical translation; experience; functional improvement; human embryonic stem cell; improved; injury and repair; lead candidate; nerve stem cell; neural; neuroregulation; nonhuman primate; programs; stem cell survival; stem cell therapy

Our work to date has demonstrated that Neural Progenitor Cells (NPCs) and Neural Stem Cells (NSCs) survive grafting to the spinal cord and extend very large numbers of axons over long distances through the lesioned rodent and non-human primate (NHP) spinal cord. Host axons also regenerate into cell grafts occupying the lesion site, and form new synaptic connections that act as neural relays across the injury to support functional improvement in both rodents and primates. We have identified a lead candidate human NSC/NPC line for clinical translation: an H9 human embryonic stem cell (a federally approved human cell line) that is driven to a spinal cord NSC/NPC fate. We refer to these cells as H9-scNSCs. H9-scNSCs survive grafting to rhesus monkey cervical spinal cord hemisection and contusion lesions. This promising line of work is advancing on a translational path, supported extensively by the VA’s RR&D Gordon Mansfield Spinal Cord Injury Consortium. We aim to bring this work to the point of readiness for human clinical trials in both subacute SCI and, subsequently, chronic SCI. In addition, our ongoing work in the Consortium aims to improve the potency of this intervention through combinations with rehabilitation and neuromodulation (e.g., targeted epidural spinal stimulation). The goal of the current application is to advance this program to submission of an FDA pre-IND, with the eventual goal of a human clinical trial of this promising approach. For the one-year funding period, this project will support project management (75% effort) and the services of a regulatory expert with experience in FDA submissions.

迄今为止，我们的工作表明神经祖细胞（NPC）和神经干细胞 （NSC）幸存于嫁接到脊髓并在长时间内延伸大量轴突 穿过病变的啮齿动物和非人类灵长类动物（NHP）脊髓的距离。主机轴突 还会再生为占据病变部位的细胞移植物，并形成新的突触连接 在损伤中充当神经继电器，以支持啮齿动物和 灵长类动物。我们已经确定了临床翻译的主要候选人NSC/NPC线： H9人类胚胎干细胞（联邦批准的人类细胞系）被驱动到脊柱 脐带NSC/NPC命运。我们将这些细胞称为H9-SCNSC。 H9-SCNSC幸存于嫁接到 恒河猴颈脊髓的脊髓半切和挫伤病变。这条有希望的线 工作正在转化道路上前进，由VA的RR＆D Gordon广泛支持 曼斯菲尔德脊髓损伤联盟。我们的目的是将这项工作达到准备就绪 亚急性SCI和随后的慢性SCI的人类临床试验。另外，我们的 财团正在进行的工作旨在通过 与康复和神经调节的结合（例如，靶向硬膜外刺激）。 当前申请的目的是将该程序提高到FDA预先提交， 以这种承诺方法进行人类临床试验的最终目标。为期一年 资助期，该项目将支持项目管理（75％的努力）和 法规经验，具有FDA提交的经验。