Projektbeschreibung
Neue niedermolekulare Wirkstoffe gegen Schizophrenie
Jüngste Forschungsergebnisse deuten darauf hin, dass das Phospholipid Lysophosphatidsäure (LPA) als synaptischer Modulator wirkt und an psychischen Erkrankungen beteiligt ist. Die Forschenden des EU-finanzierten Projekts PsychAID konnten nun zeigen, dass die Hemmung des Enzyms Autotaxin (ATX), das für die LPA-Synthese verantwortlich ist, eine geeignete Strategie zur Behandlung von Schizophrenie-Symptomen darstellt. Das Team hat inzwischen ein Patent erhalten, um Hirnerkrankungen mithilfe von niedermolekularen ATX-Hemmern zu behandeln, die auf die exzitatorische Neurotransmission einwirken. Bevor die Kommerzialisierung dieser neuen ATX-Hemmer voranschreiten kann, wird PsychAID ihr pharmakologisches Profil und ihre Wirksamkeit als neue Interventionsstrategie bei Schizophrenie bewerten.
Ziel
Within the frame of the ERC LiPsyD we have shown that recently discovered that the phospholipid LPA acts as a synaptic modulator playing a major role in regulating cortical excitability and being involved in psychiatric disorders (Trimbuch et al., 2009; Unichenko et al., 2016; Vogt et al., 2016; Vogt et al., 2017). Using specific small molecule inhibitors like PF8380, which target the LPA-synthesizing molecule autotaxin (ATX), we were able to decrease cortical hyperexcitability and to rescue disease-specific behavior in different animal models for schizophrenia to wild type (WT) levels. These results generated within the ERC LiPsyD demonstrate that ATX-inhibition is effective in treating psychiatric disorders (Vogt et al., 2016). Since current therapy for schizophrenia targeting cortical hyperexcitability is not available, ATX-inhibitors which act on excitatory neurotransmission and are effective in treating psychiatric disorders have a huge commercial potential in this 120 billion euro market (Olesen et al., 2012).
To proceed towards the commercial application of ATX-inhibitors, the PI has teamed up with Merck and was granted a patent for the use of ATX-inhibitors for brain disorders (WO 2017/071799). Briefly, the patent covers the use of the ATX-inhibitors for the therapy of brain diseases (covering psychiatric disorders like schizophrenia and eating disorders but also cerebrovascular disorders) and the use of a latest generation of ATX-inhibitors (MSC 2285264 and MSC2358829), which are comparable to the most potent currently available ATX-inhibitors, are suitable for in-vivo application and have a positive toxicological profile. However, before starting clinical trials, the pharmacological profile and the effectiveness of the novel ATX inhibitors for treatment of psychiatric disorders have to be assessed. This PoC aims therefore to the preclinical characterization of these ATX-inhibitors which is a critical step towards their commercialization
Wissenschaftliches Gebiet
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-POC - Proof of Concept GrantGastgebende Einrichtung
48149 MUENSTER
Deutschland