Development of gene therapy and cell therapy for central nervous system diseases

点击翻译按钮获取中文摘要

We have been studying the genetic and biological analysis of central nervous system(CNS)diseases, and the development of gene therapy and cell therapy for the diseases.1. Brain tumors(1)we examined-PTEN abnormality of human glioma cell lines and confirmed the deletion in human glioma cell line A172. When we transfected PTEN gene to A172, the growth was inhibited and the extension of dendrites was also suppressed. This is based on the suppression of anchorage independent cell growth by dephosphorylation of Tyr387 on focal adhesion kinase(FAK)by PTEN.(2)It is suggested that fibroblast growth factor receptor(FGFR)-2 may be one of the prognostic factors in human glioma. (3)As basic research on the development of new gene therapies, we confirmed the following findings : (1)adenovirus-mediated transfer of p33^<INGI> with p53 drastically augments apoptosis in gliomas. (2)Adenovirus-mediated overexpression of Fas induces apoptosis of gliomas. (3)Adenovirus-mediated transfer of caspase-3 with Fas ligand induces dramatic apoptosis in gliomas. (4)Adenovirus-mediated transfer of p53 and Fas ligand dramatically enhances apoptosis in gliomas. (5)Adenovirus-mediated transfer of caspase-8 augments cell death in gliomas. (6)Fiber-mutant E1B-defective adenovirus has highly augmented cytopathic effect against gliomas. (4)As clinical studies, we established human gene therapy vector producing facility, human gene therapy supportive laboratory, and surgical planning units in Nagoya University Hospital. In April 2000, we started the clinical trial of interferon gene therapy using cationic liposomes. From now, we are going to evaluate the safety and usefulness of the therapy.2. Cerebrovascular diseasesWe confirmed the usefulness of DNA repair enzyme, such as Apurinic/Apyrimidinic Endonuclease(APE), for cerebral infarction.