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，我们的工作已经证明，神经祖细胞（NPC）和神经干细胞 神经干细胞（NSC）移植到脊髓后存活下来，并在长时间内延伸出非常大量的轴突。 通过受损啮齿动物和非人灵长类动物（NHP）脊髓的距离。宿主轴突 也会再生成占据损伤部位的细胞移植物，并形成新的突触连接 作为损伤的神经中继，以支持啮齿动物和 灵长类动物我们已经确定了用于临床转化的主要候选人人NSC/NPC系： H9人类胚胎干细胞（联邦批准的人类细胞系），被驱动到脊髓 脊髓NSC/NPC的命运。我们将这些细胞称为H9-scNSC。H9-scNSC在移植后存活， 恒河猴颈脊髓半切和挫伤病变。这条前途无量的 在退伍军人事务部的RR&D Gordon的大力支持下，这项工作正在沿着一条翻译的道路前进 曼斯菲尔德脊髓损伤协会。我们的目标是使这项工作达到准备就绪的程度， 在亚急性SCI和随后的慢性SCI中的人类临床试验。另外我们 该联盟正在进行的工作旨在通过以下方式提高这种干预的效力 与康复和神经调节相结合（例如，靶向硬膜外脊髓刺激）。 当前申请的目标是将该项目推进至FDA pre-IND提交， 最终目标是对这种有前途的方法进行人体临床试验。日一年 在资助期间，该项目将支持项目管理（75%的努力）和服务， 具有FDA申报经验的监管专家。