Norwegian University of Science and Technology, Norway
Berit Johansen is professor of Biotechnology at Norwegian University of Science and Technology (NTNU), Norway; and gründer and CSO of Avexxin AS. She has a PhD in Molecular Genetics, obtained at NTNU. She has spent several periods as visiting scientist at international universities and companies, including: UCLA, Biogen Inc., University of Groningen, University of Uppsala and UCSD. Her scientific interests encompass unraveling cellular communication processes involving lipid signalling, with special emphasis on phospholipase A2 (PLA2) enzymes, including drug development targeting cPLA2. “Proof of concept” for topical treatment of psoriasis with a small molecule cPLA2 inhibitor has been achieved with. She received “Young scientist award” from European Federation of Biotechnology in 2003.
Eicosanoids, the oxygenated met abolites of arachidonic acid (AA) compri se a large family of bioactive lipids that have diverse roles in regulating homeostatic processes, in modula ting inflammation and immune responses. Phospholipase A2s (PLA2s) are a group of enzymes that hydrolyze the sn-2 position of membrane phospholipids to relea se (typically unsaturated) fatty acids, including AA, and ly sophospholipids . Three major classes of PLA2s exist in the mammalian system, including low molecular weight extracellular or secretory, sPLA2; high moleular weight calcium-independen, iPLA2; and the group IVA calcium-dependent cytosolic PLA2, cPLA2α. The latter has received the most atte ntion because it is widely expressed in nearly all mammalian cells and due to its active participation in cell metabolism. cPLA2 is identified as the the rate-limiting provider of proinf lammatory mediators, including AA, and is thus an attractive target for the development of novel antiinflammatory agents. It is found that cPLA2α plays a major role in the chronic inflammation characterizing both psoriasis and rheumatoid arthritis. Novel inhibitors showing high potency and selectivity targeting cPLA2α are developed. These represent different chemistries, thus enabling various regimes for formulation, administration and tissue accumulation. Results will be presented to demonstrate mode of action for potent cPLA2α inhibitors in relevant cellular model systems for psoriasis and rheumatoid arthritis, efficacy in animal models of disease and “Proof of concept” for treatment of human disease.