We have developed analogs of naturally occurring lipid products which provide remarkable protection to injured lungs in experimental animals and ex vivo tissue exposed to lipopolysaccharide (LPS: a component of bacterial cell walls which causes hypotension and organ injury in vivo and in cultured tissues, a mimic of sepsis) while simultaneously supporting vital organ perfusion by treating septic shock.


Working together for more than 15 years, our team has expertise in lipid chemistry, the biological effects of 20-hydroxyeicosatetraenoic acid (20-HETE) mimetics in vivo, ARDS in experimental animals and the clinical care of patient with septic ARDS.


While increasing the tension in systemic arteries thus treating dangerously low blood pressure, 20-HETE is a potent dilator of pulmonary arteries. These twin qualities position mimetics of this lipid optimally to treat ARDS since decreasing pulmonary vascular resistance and increasing systemic vascular resistance promotes flow through the heart and to the lungs.


Our preliminary and published data demonstrate improved survival of mice and lessened hypotension in rats treated with LPS and a 20-HETE mimetic. We have also demonstrated protection of ex vivo lung and pulmonary arteries injured by LPS or hypoxia (low oxygen) by 20-HETE mimetics. 20-HETE mimetics protect from ischemic lung injury in vivo, all supporting the hypothesis that 20-HETE mimetics are uniquely beneficial in protecting from lung injury as well as end organ perfusion in septic ARDS.


We hypothesize that a 20-HETEmimeticwill be effective in preventing LPS induced lung injury and provide an urgently needed new therapy for septic ARDS. Our approach is based on economical and proven technology to systematically study the structure activity relationship (SAR) of stable derivatives of 20-HETE by replacing the labile carboxylic group with appropriate bio-isosteres


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