Within the frame of the ERC-AdG LiPsyD we have shown that recently discovered synaptic modulators like lysophosphospholipid acid (LPA) play a major role in regulating cortical excitability. Using specific small molecule inhibitors, which target the LPA-synthesizing molecule autotaxin (ATX), we were able to decrease cortical hyperexcitability and to rescue specific behaviors in different animal models for psychiatric and eating disorders to control levels. Results generated within the ERC PoC PsychAiD demonstrate that ATX-inhibition in the mouse brain is effective, without apparent adverse events, is well tolerated over longer period of times, and can be achieved by brain-entering ATX-inhibitors which can be applied via the oral route. This paves the road for a full preclinical (regulatory) development of our custom designed ATX-inhibitors which show favourable in-vivo properties in the mouse in order to proceed to a clinical phase I/IIa study. Given the fact that therapies for psychiatric and eating disorders have not experienced relevant progress during the last decades, and novel treatment options are thus an urgent medical need, ATX-inhibitors which act in the brain on information processing and show efficacy in proof-of-concept studies have a huge commercial potential in this 120 billion euro market.
