부산대학교 도서관

Schizophrenia drug discovery has been a series of failures since the development of dopamine D2 receptors agents. These agents have some effect on schizophrenia, but not enough. One reason for this is estimated to be that although schizophrenia is diagnosed based on the psychological symptoms, there are multiple underlying biological dysfunctions. Recent advances in molecular biology have facilitated genome analysis, and many genes associated with schizophrenia have been reported. Thus, based on this data, we have embarked on developments of precision drug discovery for schizophrenia using model animals with the genetic mutations. The GWAS meta-analysis was shown that UGT1A1 gene mutation is a risk factor for the schizophrenia (Prata 2019). We demonstrated hyper serotoninergic transmission to the frontal cortex in the rat model, On the other hand, the dopaminergic transmission was intact (Miura 2022). Based on the findings, we developed a novel anti-psychotic agent (TRM001) for UGT1A1 gene mutations associated schizophrenia. We demonstrated that TRM001 administration rapidly ameliorates abnormal behavior in the model rat. TRM001 has been shown to be safe in healthy subjects. UGTA1 gene mutations associated schizophrenia can be easily diagnosed by genetic mutations and indirect bilirubin concentration in the blood. Since it is also possible to select patients with UGTA1 gene mutations associated schizophrenia, TRM001 could be worthy of proceeding to second clinical trials.