Development of Novel Biomarkers for Traumatic Brain injury

描述(由申请人提供)：在美国，每年至少有140万人因创伤性脑损伤(TBI)而寻求医疗救治。其中75%到90%是轻度或中度伤害。这些会对身体、认知和心理社会功能造成严重和持久的损害。创伤性脑损伤的身体、社会和经济后遗症可能会持续受害者的一生，这是个人、家庭和社会承担的负担。然而，轻中度颅脑损伤的诊断具有挑战性。常规方法，如成像和神经学检查，往往对轻微损伤不敏感。目前还没有基于血液的诊断工具来帮助临床医生诊断轻、中度脑外伤。然而，这样一种快速、可靠和灵敏的工具将极大地改善对脑外伤患者的诊断和分类，将更准确地指导治疗和管理选项，因此将在降低管理成本的同时改善患者结局。Banyan Biomarkers Inc.已被公认为开发超灵敏脑损伤生物标记物诊断分析的先驱。我们承诺向市场提供这样一种工具，基于专利的TBI生物标记物。此前，在我们的第一阶段SBIR项目中，成功地开发了一种灵敏的定量脑损伤生物标志物(BA0123)的ELISA方法，并从临床前研究中获得了证实脑损伤后脑脊液中BA0123增加的概念验证数据。随后，发现了第二个互补的神经生物标志物(BA0252)，并建立了检测其敏感性的特异性ELISA法。产生了概念验证数据，以支持这一假设，即重型脑外伤患者的脑脊液和血清中这两个生物标志物都增加了，初步数据显示，在轻、中度脑外伤患者中也检测到了这些标记物。支持开发这两种生物标志物作为辅助诊断脑外伤的工具的数据非常有说服力。在该项目的第二阶段，将开发一种可商业化的两种生物标记物(BA0123和BA0252)的酶联免疫吸附试验试剂盒。检测组件(抗体和抗原)将在充足的供应和有质量保证的条件下生产。可行性数据将从重型、中度和轻度颅脑损伤的临床研究中收集，这些研究将使生物标记物水平与损伤严重程度、疾病进展和结果的临床测量相关联。生物标志物可以区分损伤程度的准确性，以及可能进展和结果较差的患者将被评估。这项分析将确定单独或联合使用标志物BA0123和BA0252的敏感性和特异性。这些数据将用于支持FDA的IDE前应用程序。这一第二阶段项目的成果是脑损伤生物标志物的两种有质量保证的ELISA法，为其商业化奠定了基础。这些检测将被用于分析临床样本，进一步证实生物标记物作为工具用于帮助诊断重度、轻度和中度脑外伤。 在美国，每年至少有140万人患有脑损伤，其中约5万人死亡，23.5万人住院，110万人接受治疗并从急诊科出院。目前用于评估脑损伤的存在和严重程度的方法，基于CT扫描或MRI等成像技术，价格昂贵，不可靠，不是普遍可用的，而且产生结果的速度很慢。Banyan Biomarkers正在为脑损伤开发快速、可靠、敏感和经济的血液测试，这将极大地提高诊断和分类能力，将更准确地指导治疗方案，从而改善患者的预后。

DESCRIPTION (provided by applicant): Each year in the United States at least 1.4 million people seek medical attention for a traumatic brain injury (TBI). Between 75% and 90% of these are mild or moderate injuries. These can inflict profound and persistent impairment of physical, cognitive, and psychosocial functioning. The physical, social and economic sequelae of TBI can persist for the victim's entire life, a burden that is borne by the individual, their family, and by society. However, mild and moderate TBI is challenging to diagnose. Conventional methods such as imaging and neurological examination are often insensitive to mild injury. There is no blood- based diagnostic tool to aid clinicians in the diagnosis of mild and moderate TBI. However, such a rapid, reliable, and sensitive tool would greatly improve diagnosis and triage of TBI patients, would more accurately guide treatment and management options, and therefore would improve patient outcome while reducing management costs. Banyan Biomarkers Inc. has been recognized as a pioneer in the development of ultra-sensitive brain injury biomarker diagnostic assays. We have the commitment to providing such a tool to the marketplace, based on proprietary TBI biomarkers. Previously, in our Phase I SBIR project, a sensitive ELISA for quantifying one brain injury biomarker (BA0123) in CSF was successfully developed, and proof-of-concept data confirming that BA0123 is increased in CSF following brain injury was obtained from preclinical studies. Subsequently, a second complementary neuro-biomarker (BA0252) was discovered and a specific ELISA assay for its sensitive detection was developed. Proof-of-concept data to support the hypothesis that both biomarkers are increased in CSF and serum of human patients with severe TBI was generated and preliminary data show detection of these markers also in mild and moderate TBI patients. The data supporting the development of both biomarkers as tools to aid in the diagnosis of TBI are very compelling. In Phase II of this project a commercializable ELISA assay kit for both biomarkers (BA0123 and BA0252) will be developed. Assay components (antibodies and antigens) will be produced in abundant supply and under quality assured conditions. Feasibility data will be collected from clinical studies of severe, moderate, and mild TBI that will allow correlation of biomarker levels to clinical measures of injury severity, disease progression, and outcome. The accuracy with which the biomarkers can discriminate magnitude of injury, and patients that are likely to have poor progression and outcome will be evaluated. This analysis will determine the sensitivity and specificity of markers BA0123 and BA0252 when used singularly or in combination. These data will be used to support a pre-IDE application to the FDA. The deliverables of this Phase II project are two quality-assured ELISA assays for the brain injury biomarkers establishing the foundation toward their commercialization. These assays will be used to analyze clinical samples, further confirming the use of the biomarkers as tools to aid in the diagnosis of severe, mild and moderate TBI. Each year in the United States at least 1.4 million people sustain a TBI, of which about 50,000 die, 235,000 are hospitalized, and 1.1 million are treated and released from an emergency department. Current methods used to assess the existence and severity of brain injury, based on imaging techniques such as CT scanning or MRI, are expensive, not consistently reliable, not universally available, and are slow to produce results. Banyan Biomarkers is developing rapid, reliable, sensitive, and economical blood tests for brain injury that would greatly improve diagnostic and triage capabilities, would more accurately guide treatment options, and therefore would improve patient outcome.