Adduct Dipstick for Diagnosis of Acetaminophen Toxicity

描述（由申请人提供）：对乙酰氨基酚（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会导致急性肝衰竭，是美国急性肝衰竭的主要原因。目前用于诊断APAP毒性的实验室检测，即测量外周血中APAP水平，仅在APAP过量的前24小时有效。对乙酰氨基酚毒性诊断（ATD）有限责任公司开发了一种用于测量APAP蛋白加合物的快速、即时诊断试验（试纸）。加合物是APAP肝毒性的敏感和特异性生物标志物，可在APAP中毒过量后6至7天在外周血中检测到。该试纸通过使用检测系统中针对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。该量尺可靠、准确，可快速提供结果。在Specific Aim 1中，将对该量尺进行校准，以检测与严重肝毒性相对应的APAP蛋白加合物水平，并将生产2000个精密制造的研究用量尺。在特异性目标2中，将使用储存的冷冻临床样品对试纸进行内部稳定性、特异性和诊断敏感性测试。在Specific Aim 3中，六个主要的肝病学中心将参与一项研究，以测量急性肝损伤和急性肝衰竭患者的油尺性能。这些目标的成功完成将建立试纸的临床实用性，这一创新将提高APAP毒性的诊断。

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.