Neural Stem Cell Extracellular Vesicle Treatment for Traumatic Brain Injury

项目摘要/摘要 创伤性脑损伤是一种普遍关注的健康问题，被称为“无声流行病”。每年 在美国，253万患者在经历了脑外伤后去急诊科就诊，其中5.68万人死亡， 超过28.8万人需要住院、康复计划和长期支持性护理。尽管 一次创伤性脑损伤事件通常是急性、继发性损伤反应(神经炎症)和慢性 组织丢失通常会导致终生的功能缺陷。目前，还没有神经保护性或 再生食品和药物管理局批准了脑损伤治疗。阿鲁纳·比奥最近开发了一部小说 神经保护和再生神经干细胞胞外囊泡(NSCEV)产品名为AB126™ 可用于治疗颅脑损伤。AB126™对不同物种(老年人)显示出多模式治疗效果 小鼠、大鼠、猪)和神经损伤模型(脑外伤、中风)。在脑外伤啮齿动物模型中，AB126™缩小了病变大小， 促进内源性神经生成和血管生成，并迅速减轻运动功能损害。 大型动物试验一再被学术界、工业界和政府机构确定为关键 降低脑损伤治疗发展中的风险。为此，这项提案概述了FDA在猪身上进行的研究 使用临床相关评估工具建立受控皮质撞击脑损伤模型以评估其疗效和安全性 应用AB126™治疗脑外伤。这项研究的成功完成将提供以下关键信息 至AB126™剂量，对颅脑损伤的病理生理(水肿、出血)和功能结果的治疗效果， 毒性和潜在的副作用，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.