Neural Stem Cell Extracellular Vesicle Treatment for Traumatic Brain Injury

神经干细胞胞外囊泡治疗脑外伤

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要/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，有253万患者遭受了遭受TBI的急诊室，其中56,800人死亡和超过288,000人需要住院，康复计划和长期支持护理。虽然原发性TBI事件通常是急性，随后的继发损伤反应（神经炎症）和慢性组织损失通常会导致持续一生的功能缺陷。目前，没有神经保护或再生食品药物管理局批准了TBI治疗。 Aruna Bio最近开发了一部小说神经保护和再生神经元干细胞外囊泡（NSC EV）产品称为AB126™ 可用于治疗TBI。 AB126™已证明了不同物种的多模式治疗效率（老年）小鼠，大鼠，猪）和神经损失模型（TBI，中风）。在TBI啮齿动物模型中，AB126™减少病变大小，内源性神经发生和血管生成增强，运动功能障碍迅速减弱。大型动物测试已被学术，工业和政府机构反复确定为关键 TBI治疗开发的疾病风险步骤。为此，该提案概述了FDA为猪提供研究使用临床相关的评估工具来控制皮质影响TBI模型，以评估效率和安全性 AB126™作为TBI的治疗方法。这项研究的成功完成将提供有关的关键信息至AB126™剂量，对TBI病理生理学（水肿，出血）和功能结果的治疗作用，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试验。