Sepsis or septic shock is a complex cascade of adverse host systemic inflammatory responses induced by infection. Severe sepsis is the most common type found in the intensive care unit (ICU) and it is a common, frequently fatal and expensive disease. In fact, severe sepsis is the number one cause of death in the non-coronary ICU and the 11th leading cause of death overall in the United States (US). Recent studies report that there are at least 750,000 new cases of severe sepsis annually in the US with more than 2,000 new cases per day. Progression of sepsis can lead to organ dysfunction and ultimately death. Mortality from severe sepsis ranges from 30 to 50 percent or greater. ? ? The applicants have developed a therapeutic agent, Adeno-Vpr, which they believe has important therapeutic qualities relevant to the pathogenesis of severe sepsis. Viral Genomix, Inc. has a diverse and proprietary patent position on the use of Adeno-Vpr to treat sepsis and other inflammatory diseases. Successful completion of these Phase I studies will result in the demonstration of feasibility for using Adeno-Vpr as a novel drug to treat sepsis. The investigators will test their hypothesis through the conduct of three specific aims using staphylococcal enterotoxin B (SEB) and lipopolysaccharides (LPS) as model toxins from Gram-positive and Gram-negative bacteria, respectively. There are three specific aims: (1) to test the protective effects of Adeno-Vpr in lethal SEB and LPS challenge models in mice; (2) to investigate timing of injections Vs protective effects of Adeno-Vpr in SEB and LPS challenge models in mice; and (3) to test the protective effects of Adeno-Vpr in mice against polybacterial sepsis challenge using the cecal ligation and puncture (CLP) model. ? ? This project will test the hypothesis that Adeno-Vpr will be effective at preventing morbidity and mortality from toxin induced cytokine storm and sepsis in a murine model system. Successful completion of this proof-of-concept funding in this Phase I program will enable further testing of the applicant organization's drug candidate for sepsis in a Phase II program. ? ? ?
| Forche, Anja; Magee, P T; Magee, B B et al. (2004) Genome-wide single-nucleotide polymorphism map for Candida albicans. Eukaryot Cell 3:705-14 |
