[PS19-3C-K] Molecular Basis of Neurometabolic Diseases: From Molecule to Patient
Child neurology started during the first half of the 20th century with clinical and pathological analysis of infants and children presenting with brain dysfunction such as mental retardation, convulsive seizures and various neurosomatic disabilities. Then development of new biochemical technology followed, leading to discoveries of unanticipated metabolic errors mainly in neurodegenerative diseases. Analysis of the protein and gene has become a powerful tool for investigation of molecular events in individual patients with diseases of unknown etiology. More than 7,000 single gene disorders are currently listed in the McKusick’s catalog of inherited diseases. Many of them present with progressive neurological manifestations, and single gene mutations result in loss of enzyme activity and diverse phenotypic manifestations. At present, we can make diagnosis of patients and heterozygous carriers by gene mutation analysis. However, even with plenty of information about phenotypes and molecules in individual patients, we do not know much about pathogenesis of individual diseases, and treatment is not possible particularly for brain damage. I therefore started trying to elucidate the pathophysiology of neuronopathic lysosomal diseases. I will close my talk by summarizing results of my recent investigations on a new molecular therapeutic approach to a few lysosomal diseases (chaperone therapy). This experimental trial disclosed unexpected molecular events in pathological cells and tissues. I hope to step up in the near future to human patients toward my final goal of molecular therapy of inherited neurometabolic diseases.