Adduct Dipstick for Diagnosis of Acetaminophen Toxicity

说明(申请人提供)：扑热息痛(APAP)是当今世界上最常用的治疗疼痛和发烧的药物。在大剂量下，APAP会导致急性肝功能衰竭，是美国急性肝功能衰竭的主要原因。目前诊断APAP毒性的实验室测试，即外周血中APAP水平的测量，仅在APAP过量服药的前24小时有效。对乙酰氨基酚毒性诊断(ATD)，LLC已开发出一种快速、临床点诊断分析(DIPSTK)，用于测量APAP蛋白加合物。加合物是APAP肝毒性的敏感和特异的生物标志物，可在APAP中毒过量后6至7天在外周血中检测到。试纸条通过使用检测系统中加合物的特异性抗体来检测与蛋白质(APAP蛋白加合物)不可逆结合的APAP。该试纸可靠、准确，并能快速得出结果。在具体目标1中，将对试纸进行校准，以检测与严重肝脏毒性相对应的APAP蛋白质加合物的水平，并将生产2000种精密制造的研究用试纸。在特定目标2中，将使用储存的、冷冻的临床样本在内部测试试纸的稳定性、特异性和诊断敏感性。在具体目标3中，六个主要肝病中心将参与一项研究，以衡量急性肝损伤和急性肝功能衰竭患者的检测结果。成功完成这些目标将确立试纸的临床实用价值，这是一项将提高APAP毒性诊断的创新。

DESCRIPTION (provided by applicant): Acetaminophen (APAP) is the most commonly used drug for the treatment of pain and fever in the world today. In large doses, APAP causes acute liver failure and is the leading cause of acute liver failure in the US. The current laboratory test for the diagnosis of APAP toxicity, measurement of APAP levels in peripheral blood, is only effective in the first 24 hours of APAP overdose. Acetaminophen Toxicity Diagnostics (ATD), LLC has developed a rapid, point-of-care diagnostic assay (dipstick) for the measurement of APAP protein adducts. Adducts are sensitive and specific biomarkers of APAP hepatotoxicity that may be detected in peripheral blood 6 to 7 days after a toxic overdose of APAP. The dipstick detects APAP irreversibly bound to proteins (APAP protein adducts) by using antibodies specific for adducts in the detection system. The dipstick is reliable, accurate and provides rapid results. In Specific Aim 1, the dipstick will be calibrated to detect levels of APAP protein adducts corresponding to severe liver toxicity and 2000 precision manufactured, research use dipsticks will be produced. In Specific Aim 2, the dipsticks will be tested internally for stability, specificity, and diagnostic sensitivity using stored, frozen clinical samples. In Specific Aim 3, six major hepatology centers will participate in a study to measure dipstick performance in patients with acute liver injury and acute liver failure. Successful completion of these aims will establish the clinical utility of the dipstick, an innovation that will enhance the diagnosis of APAP toxicity.