Descrizione del progetto
Nuovi farmaci a piccole molecole contro la schizofrenia
Evidenze recenti indicano che il fosfolipide acido lisofosfatidico funge da modulatore sinaptico ed è implicato nei disturbi psichiatrici. Gli scienziati del progetto PsychAID, finanziato dall’UE, hanno dimostrato che l’inibizione dell’enzima autotaxina, che sintetizza l’acido fosfolipidico, può essere utilizzata come strategia per affrontare i sintomi della schizofrenia. I ricercatori hanno ottenuto un brevetto per trattare i disturbi cerebrali utilizzando inibitori dell’autotaxina a piccole molecole che agiscono sulla neurotrasmissione eccitatoria. Prima di passare alla commercializzazione di questi nuovi inibitori dell’autotaxina, PsychAID valuterà il proprio profilo farmacologico e la propria efficacia come nuova strategia d’intervento per la schizofrenia.
Obiettivo
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
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-POC - Proof of Concept GrantIstituzione ospitante
48149 MUENSTER
Germania