SERUM MAP-TAU IN TRAUMATIC BRAIN INJURY

该I期申请的目的是开发一种基于血清的急性神经元变性生物标志物。该试验用于评估几种临床适应症，包括创伤性脑损伤（TBI），以及评估神经保护剂疗效的替代终点。我们开发了一种夹心ELISA，用于定量神经元定位蛋白MAP-tau，它是从受损神经元中释放出来的。利用这种MAP-tau酶联免疫吸附试验，我们发现脑损伤患者脑脊液（CSF）中MAP-tau水平升高了10,000倍。在初步研究中，我们发现脑外伤患者的血清MAP-tau水平比对照组高40倍。拟议的研究将评估通过量化血清MAP- tau水平来测量脑外伤患者神经元损伤的临床可行性。具体目的1：确定与神经系统对照组（N=30）和非神经系统对照组（N=30）相比，TBI患者（N=30）的血清MAP-tau水平是否升高。特异性目的2：确定TBl患者血清MAP-tau水平升高的时间过程（N=15）。特异性目的3：确定血清MAP-tau的升高是否与脑脊液MAP-tau通过受损的血脑屏障扩散到血液中的损伤相关升高有关。拟议的商业应用：该I期申请的目标是开发一种基于血清的急性神经元变性生物标志物。该试验用于评估几种临床适应症，包括创伤性脑损伤（TBl），以及评估神经保护剂疗效的替代终点。

The objective of this Phase I application is to develop a serum-based biomarker for acute neuronal degeneration. This test is needed to assess several clinical indications including traumatic brain injury (TBI), as well as, a surrogate endpoint for assessing the efficacy of neuroprotective agents. We have developed a sandwich ELISA for quantifying a neuronally localized protein, MAP-tau, that is released from damaged neurons. Employing this MAP-tau ELISA, we have shown that MAP-tau cerebrospinal fluid (CSF) levels are elevate 10,000 fold in TBI patients. In preliminary studies, we demonstrate that serum MAP-tau levels are elevated 40 fold in TBI patients compared to controls. The proposed studies will assess the clinical feasibility of measuring neuronal damage in TBI patients by quantifying serum MAP- tau levels. The Specific Aims are: Specific Aim 1: Determine if serum MAP-tau levels are elevated in TBI patients (N=30) compared to neurologic controls (N=30) and non-neurologic controls (N=30). Specific Aim 2: Determine the time course of elevated serum MAP-tau levels in TBl patients (N=15). Specific Aim 3: Determine if the elevation of serum MAP-tau is associated with an injury-related elevation in CSF MAP-tau that diffuses into blood via a compromised blood brain barrier. PROPOSED COMMERCIAL APPLICATIONS: The objective of this Phase I application is to develop a serum-based biomarker for acute neuronal degeneration. This test is needed to assess several clinical indications including traumatic brain injury (TBl), as well as, a surrogate endpoint for assessing the efficacy of neuroprotective agents.