Studies of inherited neurodegenerative disease ; mutation analysis and gene therapy

点击翻译按钮获取中文摘要

We investigated the mutation analysis and gene therapy for neurodegenerative disorders caused by enzyme defect. We identified and genotyped a patient with neuronopathic Gaucher disease (GD) presenting unique phenotype, hydrocephalus, valvur calcification and corneal opacities. This patient was homozygous for D409H mutation. We performed pathological examinations of a patient with type 2 GD treated with enzyme replacement therapy. This study suggest that gene therapy using neurotropic vector should be required for treating type 2 GD.We produced recombinant adenovirus that express human glucuronidase and this recombinant adenovirus to animal model intravenously. Pathological abnormalities in liver and spleen were improved, and the urinary glycosaminoglycans were also reduced in treated mice. Transduction of enzyme into brain was seen only by adminstration of direct injection of recombinant adenovirus into the lateral ventricles. We succeeded in efficient transferring glucuronidase gene in a retroviral vector to human hematopoietic progenitor cells. These data provide encouragement that gene therapy for neurodegenerative disorders caused by enzyme defect is efficacious.