Neural Stem Cell Extracellular Vesicle Treatment for Traumatic Brain Injury

项目概要/摘要 创伤性脑损伤（TBI）是一个普遍的健康问题，被称为“沉默的流行病”。每年 在美国，253万名患者在遭受TBI后前往急诊室，其中56，800人死亡， 超过288，000人需要住院治疗、康复计划和长期支持性护理。虽然 原发性TBI事件通常是急性的，随后的继发性损伤反应（神经炎症）和慢性的 组织损失通常导致持续一生的功能缺陷。目前，没有神经保护或 再生食品和药物管理局批准的创伤性脑损伤治疗。Aruna Bio最近开发了一种新的 神经保护和再生神经干细胞细胞外囊泡（NSC EV）产品，称为AB 126 ™， 可用于治疗TBI。AB 126 ™已在不同物种（老年人）中证明了多模式治疗功效。 小鼠、大鼠、猪）和神经损伤模型（TBI、中风）。在TBI啮齿动物模型中，AB 126 ™减小了病变尺寸， 增强内源性神经发生和血管生成，并迅速减弱运动功能障碍。 大型动物试验已多次被学术界、工业界和政府机构确定为关键 降低TBI治疗开发的风险。为此，该提案概述了FDA在猪中的支持研究 使用临床相关评估工具评价有效性和安全性的受控皮质撞击TBI模型 的AB 126 ™作为TBI的治疗。本研究的成功完成将提供有关以下方面的关键信息 AB 126 ™剂量、对TBI病理生理学（水肿、出血）和功能结果的治疗效果， 毒性和潜在的不良副作用，将作为IND提交和未来临床的基础 审判

Project Summary/Abstract Traumatic brain injury (TBI) is a universal health concern and is known as a “silent epidemic”. Each year in America, 2.53 million patients visit the emergency department after suffering a TBI of which 56,800 die and over 288,000 require hospitalization, rehabilitation programs, and long-term supportive care. Although the primary TBI event is typically acute, subsequent secondary injury responses (neuroinflammation) and chronic tissue loss often result in functional deficits that last a lifetime. Presently, there are no neuroprotective or regenerative Food and Drug Administration approved TBI treatments. Aruna Bio has recently developed a novel neuroprotective and regenerative neural stem cell extracellular vesicle (NSC EV) product called AB126™ that may be used to treat TBI. AB126™ has demonstrated multimodal therapeutic efficacy in divergent species (aged mouse, rat, pig) and neural injury models (TBI, stroke). In TBI rodent models, AB126™ reduced lesion sizes, enhanced endogenous neurogenesis and angiogenesis, and rapidly attenuated motor function impairments. Large animal testing has been repeatedly identified by academic, industry, and government agencies as a key de-risking step in TBI therapeutic development. To this end, this proposal outlines FDA enabling studies in a pig controlled cortical impact TBI model using clinically relevant assessment tools to evaluate the efficacy and safety of AB126™ as a treatment for TBI. The successful completion of this study will provide key information pertaining to AB126™ dosage, therapeutic effects on TBI pathophysiology (edema, hemorrhage) and functional outcomes, toxicity, and potential adverse side effects that will serve as the basis for an IND submission and future clinical trials.