Abstract

iPSC-based Cell Therapy and Modeling of Neural Disorders

Hideyuki Okano, Professor, Department of Physiology, Keio University School of Medicine

What makes the investigation of human psychiatric/psychiatric disorders so difficult? This could be attributed to the following reasons 1) Diseases model mice do not always recapitulate the pathophysiology of human diseases, 2) It is extremely difficult to investigate what is taking place in vivo at the onset of the disease due to the low accessibility to the pathological foci in the brain, and 3) The responsible neuronal circuits for the phenotype are not identified. In order to overcome these difficulties, we took advantage of iPS cell technologies and transgenic non-human primates for modeling human psychiatric/psychiatric disorders. So far, we have established iPS cells from the patients of about 40 human psychiatric/psychiatric disorders and characterized their pathophysiology, including Alzheimer disease, Parkinson disease, ALS, Rett syndrome (and Pelizaues-Merzbacher disease. I will talk about how we are developing new drugs for ALS using iPS cells technology. Furthermore, for faithfully modeling the human psychiatric/psychiatric disorders in vivo, we developed transgenic non-human primates (common marmosets) with germline transmission. In the present talk, we also wish to mention our recent data of generation of common marmoset transgenic models of neurodegenrerative diseases, including Parkinson disease. Furthermore, we have done the deep sequencing of marmoset whole genome with NGS could generate knock-out technologies of common marmoset using genome editing technologies for the generation of transgenic marmoset model of autism and psychiatric disorders.