WAVE1 INHIBITION IN THE MEDICAL INTERVENTION OF INFLAMMATORY DISEASES AND/OR INFECTIONS CAUSED BY A PATHOGEN

摘要

The present invention relates to antagonists/inhibitors of WAVE1 (Wiskott Aldrich syndrome protein-family verprolin-homologous protein 1) for use in the prevention or treatment of an infection caused by a pathogen and/or in the prevention or treatment of an oxidized phospholipids (OxPL) related inflammatory disease developing in response to an infection caused by a pathogen. Moreover, the present invention relates to the prevention of secondary infections subsequent to an insult, like injury, surgery, trauma or inflammation wherein said insult leads to elevated level of oxidized phospholipids in vivo. Furthermore, antagonists/inhibitors of WAVE1 are comprised that are co-administered with antibiotics, antiviral drugs, antioxidants and/or anti-inflammatory drugs. In a further aspect, the present invention provides for a method for assessing the activity of a candidate molecule suspected of being an antagonist/inhibitor of WAVE1 comprising the steps of: (a) optionally preincubating a cell, tissue or a non-human animal comprising and expressing WAVE1 with OxPL; (b) contacting said cell, tissue or a non-human animal comprising WAVE1 with said candidate molecule; (c) detecting a decrease in WAVE1 activity; and (d) selecting a candidate molecule that decreases WAVE1 activity; wherein a decrease of the WAVE1 activity is indicative for the capacity of the selected molecule to ameliorate, prevent or treat an OxPL related to an inflammatory disease developing in response to an infection caused by a pathogen and/or prevent, ameliorate or treat an infection caused by a pathogen and/or prevent an infection subsequent to a physiolgical insult like injury, trauma, surgery or inflammation. In yet another aspect, the present invention provides for a cell, tissue or a non-human animal for screening and/or validation of a compound suspected of being an antagonist/inhibitor of WAVE1. Finally, a kit is provided that is useful for carrying out the method of the invention comprising polynucleotides and/or antibodies capable of detecting the activity of WAVE1.