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）寻求医疗护理。其中75%至90%为轻度或中度损伤。这些疾病会对身体、认知和心理社会功能造成深刻和持久的损害。创伤性脑损伤的身体、社会和经济后遗症可能持续受害者的一生，这是个人、家庭和社会所承受的负担。然而，轻度和中度TBI的诊断具有挑战性。传统的方法，如影像学和神经系统检查往往是不敏感的轻度损伤。没有基于血液的诊断工具来帮助临床医生诊断轻度和中度TBI。然而，这种快速、可靠和灵敏的工具将极大地改善TBI患者的诊断和分诊，将更准确地指导治疗和管理选项，并且因此将改善患者结果，同时降低管理成本。Banyan Biomarkers Inc.被认为是开发超灵敏脑损伤生物标志物诊断测定的先驱。我们致力于为市场提供基于专有TBI生物标志物的此类工具。之前，在我们的I期SBIR项目中，成功开发了用于定量CSF中的一种脑损伤生物标志物（BA0123）的灵敏ELISA，并且从临床前研究中获得了确认脑损伤后CSF中BA0123增加的概念验证数据。随后，发现了第二种互补的神经生物标志物（BA0252），并开发了用于其灵敏检测的特异性ELISA测定。生成了支持两种生物标志物在患有严重TBI的人类患者的CSF和血清中增加的假设的概念验证数据，并且初步数据显示在轻度和中度TBI患者中也检测到这些标志物。支持这两种生物标志物作为辅助TBI诊断工具的数据非常引人注目。在该项目的第II阶段，将开发两种生物标志物（BA 0123和BA 0252）的可商业化的ELISA测定试剂盒。将在保证质量的条件下大量生产试验组分（抗体和抗原）。将从重度、中度和轻度TBI的临床研究中收集可行性数据，这些研究将使生物标志物水平与损伤严重程度、疾病进展和结局的临床指标相关。将评估生物标志物区分损伤程度的准确性，以及可能进展和结局不良的患者。该分析将确定标记物BA0123和BA0252单独或联合使用时的灵敏度和特异性。这些数据将用于支持向FDA提交的IDE前申请。该第二阶段项目的可交付成果是两种用于脑损伤生物标志物的有质量保证的ELISA测定法，为其商业化奠定了基础。这些检测将用于分析临床样本，进一步确认生物标志物作为工具的用途，以帮助诊断重度，轻度和中度TBI。 在美国，每年至少有140万人患有TBI，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室出院。目前用于评估脑损伤的存在和严重程度的方法，基于成像技术，如CT扫描或MRI，是昂贵的，不一致的可靠性，不是普遍可用的，并且产生结果的速度很慢。Banyan Biomarkers正在开发快速，可靠，灵敏和经济的脑损伤血液检测，这将大大提高诊断和分诊能力，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.