Sepsis is the leading cause of death in surgical intensive care units with mortality rates over 35%. Despite considerable efforts to improve therapy over the last 50 years, no significant reduction in the mortality of patients has occurred since the introduction of antibiotics. It is well recognized that lipopolysaccharides (LPS), which are the structural components of the outer membrane of gram negative bacteria, play a pivotal role in the sepsis syndrome. The toxic center of the LPS molecule is a glycolipid moiety called lipid A, whose structure is highly conserved among gram-negative bacteria and a logical target for developing therapeutics against sepsis.

Researchers at KU Medical Center have developed synthetic cationic amphiphilic molecules to bind and sequester bacterial LPS and inhibit its toxicity in vitro and in vivo. Such molecules also appear to inhibit the deleterious effects of the administration of Gram-positive organisms, presumably by sequestration and subsequent neutralization of one or more species of molecules present in Gram-positive organisms that bear some physiochemical similarities to LPS.

Advantages:
-Low cost, effective, and broad-spectrum therapeutic agents for the treatment of sepsis and septic shock
-May enhance the effect of Gram-positive and/or Gram-negative sepsis or septic shock associated with septicemia
-The agents may enhance the effect of systemic antibiotic therapy by reducing or preventing pathological sequelae

References:

AntiMicrobial Agents and Chemotherapy, April 1999, p.912-919The Journal of Infectious Diseases. 1997; 176:84-93Virology. 1998; 240: 118-126

File Number: 98KUMC177 

Other Information: *State of Development* Available for license negotiations. *Testing* Animal studies have shown that these compounds prevent recognition of LPS by monocytes/macrophages, inhibit the production of inflammatory mediators, inhibit the induction of gene transcrition log LPS, and inhibit the production of endothelial derived nitric acid.