Descripción del proyecto
Nuevos fármacos de molécula pequeña contra la esquizofrenia
Pruebas recientes indican que el fosfolípido ácido lisofosfatídico (LPA, por sus siglas en inglés) sirve como regulador sináptico y está implicado en trastornos psiquiátricos. Los científicos del proyecto PsychAID, financiado con fondos europeos, han demostrado que puede emplearse la inhibición de la enzima autotaxina (ATX) que sintetiza el LPA como estrategia para hacer frente a los síntomas de la esquizofrenia. Los investigadores han obtenido una patente para tratar los trastornos encefálicos usando inhibidores de la ATX de molécula pequeña que actúan sobre la neurotransmisión excitatoria. Antes de proceder a la comercialización de estos nuevos inhibidores de la ATX, PsychAID evaluará su perfil farmacológico y su eficacia como nueva estrategia de intervención para la esquizofrenia.
Objetivo
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
Ámbito científico
Programa(s)
Régimen de financiación
ERC-POC - Proof of Concept GrantInstitución de acogida
48149 MUENSTER
Alemania