TOKYO, April 10, 2013 - Astellas Pharma Inc. (“Astellas”; Tokyo:4503) announced today that its collaborative research project with Johns HopkinsUniversity School of Medicine (“JHU”; Baltimore) identified a novel action of quetiapine in the regulation of a cell-cycle related gene in CD-1 mice. The study results were published in Translational Psychiatry, a Nature Publishing Group journal focusing on the translational science in psychiatry between basic research and clinical.

The research team found that the chronic treatment with quetiapine, which was designed by the clinically-relevant pharmacodynamics examination of antipsychotics, uniquely down-regulated the cell-cycle related p21/Cdkn1a gene expression in the mouse frontal cortex when compared to the treatment with a typical antipsychotic haloperidol. The reduction of gene expression was observed in post-mitotic neurons and oligodendrocytes in the quetiapine treated-mice.

It is commonly accepted that the pharmacological actions of typical antipsychotics are mainly based on the blockade of dopamine D2 receptor in the striatum and could affect the positive symptoms of schizophrenia. Newly introduced atypical antipsychotics are acknowledged for additional clinical benefits. The clinical use of quetiapine in bipolar depression and major depression in addition to schizophrenia has been approved by the many countries. Although it is postulated that the modulation of neurotransmitter receptors including dopamine D2, serotonin 5HT2A, and adrenergic alpha 1 contributes to the clinical benefits of quetiapine, its affect on brain regions and intracellular functional pathways are not fully understood. The present study demonstrated that, in CD-1 mice, quetiapine regulates intracellular gene expression in both post-mitotic neurons and oligodendrocytes. In human, the aberrant regulation of cell-cycle is supported by the fact of genetic, pathological, and gene expression analyses of post-mortem brains of patients and the white matter abnormality attributable to oligodendrocyte dysfunction have been suggested as common pathophysiologies across schizophrenia, bipolar disorder, and major depressive disorder., the present discovery of a potential novel action of quetiapine in frontal cortex may shed additional light on its mode-of-action.

Astellas expects to identify new drug targets and conduct translational science research to create innovative pharmaceuticals in the field of neuroscience by building on the research reported in this paper.

 

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The title and authors of the article reported in Translational Psychiatry published on April 2, 2013 (local time) are as follows:

Title:

Unique pharmacological actions of atypical neuroleptic quetiapine:
possible role in cell cycle/fate control

Authors: Mari A. Kondo, Katsunori Tajinda, Carlo Colantuoni, Hideki Hiyama, Saurav Seshadri, Beverly Huang, Samantha Pou, Keiko Furukori, Caroline Hookway, Hanna Jaaro-Peled, Shin-ichi Kano, Nobuya Matsuoka, Katsuya Harada, Keni Ni, Jonathan Pevsner, and Akira Sawa