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Psychiatric Disorders: ATX-inhibiting drugs as a new therapeutic option: Proof-of-Concept

Objective

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
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Host institution

WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER

Address

Schlossplatz 2
48149 Muenster

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 149 375

Beneficiaries (1)

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WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER

Germany

EU Contribution

€ 149 375

Project information

Grant agreement ID: 811385

Status

Ongoing project

  • Start date

    1 January 2019

  • End date

    30 June 2020

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 149 375

  • EU contribution

    € 149 375

Hosted by:

WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER

Germany