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Description
Schizophrenia is one of the worst mental disorders that affects 1% of the entire human population. Schizophrenia is a very complex disorder with symptoms that include hallucinations, social withdrawal and IQ deterioration. The current therapy for schizophrenia consists of drugs that have limited effectiveness and, worst, induce very strong side effects. The reason for existing poor therapeutical strategy against schizophrenia is that the molecular mechanisms underlying this pathology are not yet fully understood. Therefore, our project aims to contribute to the understanding of the molecular mechanisms that take part in the onset and development of this horrendous disease. The identification of novel and previously uncharacterized genes that might to be involved in schizophrenia is one of our major objectives. The focus of this project is to discover the biological functions and contribution to schizophrenia of these three genes by employing a combination of molecular pharmacology, molecular biology, bioinformatics, and genetics. Next, we will identify chemical modulators of these three genes that can have therapeutic value in schizophrenia or other neurodevelopmental diseases.
The efforts undertaken to successfully achieve the objective of the project are shared by a Research Consortium that consists of experienced scientists from three institutions: Institute of Biochemistry, Romanian Academy, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway and “Cantacuzino” National Institute for Medico- Military Research and Development Romania. Institute of Biochemistry, Romanian Academy has expertise in molecular pharmacology and molecular biology concepts and methods, the Institute of Clinical Medicine, University of Oslo, has a long-lasting expertise in genetics and metabolomics, whereas the “Cantacuzino Institute”, Romania, has expertise in genetic models of schizophrenia.
Summary of project results
Schizophrenia is one of the most debilitating psychiatric disease affecting more than 1% of the population. Current treatment of schizophrenia is very limited and produce no real benefits for patients in terms of quality of life and symptoms alleviation. Moreover, the side effects of the current therapy for schizophrenia is very severe. The project aimed to evaluate new targets for the treatment of schizophrenia by unraveling the biological roles of three human genes with unknown functions and their possible relation to schizophrenia.
During the implementation of the project, new concepts and technologies in the area of cellular biology and murine genetics were developed and optimized. A functional screening platform was also developed. This platform allows us to test the effect of new drugs on novel receptor targets with the potential of developing new therapeutic approaches for diseases like schizophrenia. Moreover, this platform will allow us to expand our research lines to other diseases such as diabetes and neurodegeneration. A dedicated website was developed that allows general public access to our research project description and results.
The results obtained in this project are valuable to the academic community and also to the pharmaceutical industry. The discovery of a novel adrenergic system in humans with potential anti-cancer activity will definitely contribute to a better understanding of the cellular and molecular mechanisms of cancer and neurological diseases such as schizophrenia. On the other hand, the discovery of GPR75 as a major target in diabetes and its relation to psychotic conditions will also be beneficial to academia and pharmaceutical industry. Both discoveries will open new research lines in both academia and the pharma industry.
Summary of bilateral results
The bilateral collaboration was strengthened during the implementation of the project. The expertise of the Norwegian group at the Institute of Clinical Medicine at the University of Oslo on genome-wide associated studies was critical in the successful completion of the project by providing essential information on genetic variants of the genes under studies and the potential association of these variants with schizophrenia and depression. The bilateral collaboration was strengthened also by constant meetings in which scientific and managerial issues were analyzed. To maintain the collaborative work, applications for future funding are considered whenever the opportunities will occur.