Neural Stem Cell Extracellular Vesicle Treatment for Traumatic Brain Injury

神经干细胞胞外囊泡治疗脑外伤

• 批准号: 10483956
• 负责人: STEVEN L STICE
• 金额: $ 34.62万
• 依托单位: ARUNA BIOMEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10483956
• 关键词: Accident and Emergency department; Acute; Americas; Animal Testing; Area; Assessment tool; Attenuated; Brain; Cerebral hemisphere hemorrhage; Cerebrum; Chemistry; Chronic; Clinical; Clinical Trials; Data; Development; Dose; Edema; Emergency department visit; Epidemic; Evaluation; Event; Family suidae; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Goals; Government Agencies; Grant; Health; Hemorrhage; Hospitalization; Human; Impairment; Industry; Inflammation; Investigational Drugs; Investigational New Drug Application; Ischemic Stroke; KDR gene; Laboratories; Legal patent; Lesion; Magnetic Resonance Imaging; Medical; Methods; Modality; Modeling; Monitor; Motor; Mus; Neurologic; New Drug Approvals; Patients; Pharmacology; Phase; Positioning Attribute; Prevalence; Rattus; Recovery; Rehabilitation therapy; Resolution; Risk; Rodent; Rodent Model; Safety; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Stroke; Supportive care; TBI treatment; Testing; Therapeutic; Therapeutic Effect; Tissues; Toxic effect; Traumatic Brain Injury; Traumatic Brain Injury recovery; Treatment Efficacy; United States Food and Drug Administration; United States National Institutes of Health; Universities; Walking; aged; angiogenesis; animal efficacy; clinically relevant; commercialization; controlled cortical impact; dosage; efficacy evaluation; efficacy study; experience; extracellular vesicles; functional outcomes; motor function improvement; motor function recovery; multimodality; nerve injury; nerve stem cell; nestin protein; neural network; neurogenesis; neuroinflammation; neurological recovery; novel; porcine model; preclinical study; programs; regenerative; response; response to injury; side effect; stroke model; therapeutic development; white matter

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.

项目总结/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对猪的支持研究 使用临床相关评估工具评估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