Currently, the only test commercially available to measure endotoxin in biological fluids, the Limulus amebocyte lysate (LAL) assay, is FDA approved for the detection of endotoxin in human and animal parenteral drugs, biological products, and medical devices. This test is not FDA approved as a clinical diagnostic to detect endotoxin in the blood of patients at risk of gram negative septicemia because a number of interfering substances are present in blood that enhance or inhibit the LAL. In the United States, septicemia is the 13th leading cause of death, the leading cause of death, the leading cause of death in the intensive care unit, and accounts for $5 - 10 billion in annual health care expenditures. The incidence of septicemia in academic medical centers is 2 cases per 100 hospital admissions and the 28 day and 5 month mortality rate is 34% and 45%, respectively. Moreover, over 600,000 cases of septicemia were reported in 1995 and approximately 60% of these cases were caused by gram negative bacteria. Following its release from gram negative bacteria, circulating endotoxin induces a cascade of cellular and chemical events that result in organ damage, shock, and death. Following the confirmation that a ligand binding assay (LBA) is a sensitive and specific test to detect endotoxin in biological fluids (specific aim 1), using this LBA, clinical studies will be conducted to demonstrate that the detection of endotoxin in human blood is an early sensitive and specific predictor of organ dysfunction (specific aim 2). The data obtained from these studies will be used to support commercialization of a LBA as a clinical diagnostic for detection of endotoxin. The data obtained from these studies will serve as a platform for the design of clinical trials for the use of an antiendotoxin therapy for the prevention and early treatment of endotoxin-induced-organ damage in Phase III of this project to be funded by a commercial entity, strategic alliance.
Currently, there is no reliable clinical diagnostic to detect endotoxin in the blood of patients. Based on a market analysis it is estimated that the potential commercial value for this clinical diagnostic is $300 - 500 million a year.
