The goal of this project is developing a new drug for treatment of sepsis and lung edema. The lead molecules are based on a new chemical scaffold and demonstrate multiple beneficial pharmacological activities such as inhibition of systemic inflammation and prevention of fluid accumulation in lungs.
Eingereicht von: Univ. Prof. Dr. Valery Bochkov
Firma/Universität: Karl-Franzens-Universität Graz
Kooperationspartner: University of Maryland – School of Medicine – USA
The lead compounds based on the scaffold of oxidized phospholipids (OxPLs) demonstrate a unique combination of two pharmacological activities, namely i) inhibition of inflammation induced by Gram-negative and Gram-positive bacteria through Toll-like receptors 2 and 4, as well as ii) enhancement of barrier properties of endothelium in lung vessels and prevention of lung edema formation. Toll-like receptors are well known to be involved in pathogenesis of multiple diseases, including acute local and systemic inflammation, which is often accompanied by formation of lung edema. Furthermore, lung edema often develops as a consequence of other conditions of primarily non-infectious origin, such as severe trauma. Although the total incidence of such conditions worldwide represents hundreds of thousands of cases per year, an effective ethiological treatment for such pathologies is still missing. We expect that a unique polypharmacology of drugs based on the OxPL scaffold can improve current therapy in systemic inflammation and lung edema.