NEW YORK (Reuters Health) Sept 13 - DS-96, a specifically designed synthetic agent, binds lipopolysaccharide (LPS) and neutralizes its toxicity, according to researchers at the University of Kansas, Lawrence. It also appears to be safe.
"The potency of DS-96 in vitro and in animal models of sepsis renders this an attractive candidate for further preclinical development," senior investigator Dr. Sunil A. David told Reuters Health.
In the August issue of Antimicrobial Agents and Chemotherapy, Dr. David and colleagues note that LPS, or endotoxin, a structural component of gram-negative bacterial outer membranes, plays a key role in the pathogenesis of septic shock.
Although the peptide antibiotic polymyxin B can sequester LPS and abrogate its toxicity, the agent itself it is too toxic for systemic use. Based on a nuclear magnetic resonance-derived model of polymyxin B-LPS complex, the team developed DS-96, which binds LPS and neutralizes its toxicity without causing any apparent harm.
The researchers found that DS-96 was protective in mice given the agent before hitherto lethal challenge with LPS. DS-96 had no effect when given after challenge. However, concluded Dr. David, "a drug that could be given prophylactically to patients at risk would significantly decrease the incidence of this frequently fatal disease."
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