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%到90%是轻度或中度损伤。这些会对身体、认知和社会心理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伴随受害者的一生，这是个人、家庭和社会共同承担的负担。然而，轻度和中度创伤性脑损伤的诊断具有挑战性。影像学和神经学检查等常规方法往往对轻度损伤不敏感。目前还没有基于血液的诊断工具来帮助临床医生诊断轻度和中度TBI。然而，这种快速、可靠、灵敏的工具将极大地改善TBI患者的诊断和分诊，更准确地指导治疗和管理方案，从而在降低管理成本的同时改善患者的预后。Banyan生物标志物公司已被公认为开发超敏感脑损伤生物标志物诊断分析的先驱。我们致力于为市场提供这样一种基于专有TBI生物标志物的工具。此前，在我们的I期SBIR项目中，成功开发了一种用于定量脑脊液中一种脑损伤生物标志物（BA0123）的敏感ELISA，并从临床前研究中获得了确认脑损伤后脑脊液中BA0123增加的概念验证数据。随后，第二种互补的神经生物标志物（BA0252）被发现，并开发了一种特异性的ELISA检测方法。产生了概念验证数据，以支持这两种生物标志物在严重TBI患者的脑脊液和血清中增加的假设，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诊断工具的数据是非常令人信服的。在该项目的第二阶段，将开发用于这两种生物标志物（BA0123和BA0252）的商业化ELISA检测试剂盒。化验成分（抗体和抗原）将在充足的供应和有质量保证的条件下生产。可行性数据将从重度、中度和轻度TBI的临床研究中收集，这些研究将允许生物标志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。将评估生物标志物区分损伤程度的准确性，以及可能有不良进展和结果的患者。该分析将确定BA0123和BA0252标记物单独使用或联合使用时的敏感性和特异性。这些数据将用于支持向FDA提交ide前申请。该二期项目的成果是两个有质量保证的脑损伤生物标志物ELISA检测，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辅助诊断重度、轻度和中度脑外伤的工具的使用。

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.