Building academic-industrial alliances to stimulate drug discovery for psychiatric diseases

Abstract

Most pharmaceutical companies have ceased drug discovery programs targeting psychiatric diseases given many costly failures in the last decades. Nonetheless, there is still a strong demand in novel pharmaceutical approaches since many symptoms e. g. of schizophrenia cannot be targeted adequately. Therefore, early stage academic-industrial collaborations may offer an opportunity to address novel targets in schizophrenia and to develop and validate novel lead compounds. It has been widely accepted that Schizophrenia is likely to be a neurodevelopmental disease associated with a strong genetic component. More recently, human genetics has provided a plethora of genetic risk factors for Schizophrenia. Tailor-made transgenic animal models of individual risk factors represent promising tools to unravel the neurobiological functions of these risk factors at the developmental, cellular and systemic level. Dedicated animal models also allow for the targeted preclinical validation of novel therapeutic approaches up to behavioral consequences which are usually not accessible for the industry. In this symposium, early stage academic-industrial drug discovery approaches targeting the Neuregulin1-ERBB4 risk pathway will be presented. In a drug repurposing approach, Spironolactone was identified in a cell-based screen with clinically approved substances as a novel ERBB-inhibitor that can ameliorate behavioral deficits in mice that display increased Neuregulin1-ERBB4 signaling. These results led to the initiation of a clinical trial to assess Sprionolactone as a potential add-on therapy for schizophrenia. Moreover, academic-industrial collaborations have been fostered to develop novel lead compounds targeting Neuregulin1-ERBB4 signaling. In summary, this symposium will highlight the importance of well characterized animal models to understand the function of risk genes/pathways and their value to validate treatment options focused on neurobiological risk mechanisms of Schizophrenia.