STUDIES ON THE MECHANISM OF PATHOGENESIS OF THE MUCOPOLYSACCHARIDOSES

粘多糖症发病机制的研究

• 批准号: 4696879
• 负责人: G CONSTANTOPOULOS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4696879
• 关键词: antiprotozoal agents; astrocytes; axon; beta glucuronidase; brain; child (0-11); disease /disorder model; enzyme structure; enzyme therapy; gangliosides; human subject; human tissue; inborn lipid storage disorder; inborn lysosomal enzyme disorder; lysosomes; mental retardation; mucopolysaccharides; mucopolysaccharidosis; mucopolysaccharidosis type I; mucopolysaccharidosis type II; mucopolysaccharidosis type III; neurochemistry; neurophysiology; pathologic process; sphingolipids; tissue /cell culture

The mucopolysaccharidoses (MPS) are a group of hereditary diseases characterized by defective metabolism of glycosaminoglycans (GAG). The disorders are usually associated with severe dysfunction of the nervous system as well as of liver, spleen, heart, bone, and other tissues. Objective of this project is the study of mechanism of pathogenesis of these diseases with emphasis on brain involvement and mental retardation. We are using a comparative approach. For this purpose we study the changes, in GAG, sphingolipids, and pertinent lysosomal enzymes in tissues of patients with various types of MPS and we make correlation in terms of clinical and ultrastructural findings. Our laboratory contributed significantly in understanding the chemical pathology and in particular the neurochemistry of MPS IH, MPS IS, MPSII, MPSIII A and MPS III B. To complement the studies with human subjects, a drug (suramin) indiced animal model of MPS has been developed and a canine model, (natural), of MPS 1 is being studied. Both animal models may prove useful for understanding the pathogenesis of MPS and in the development an assessment of therapeutic trials by enzyme replacement.

粘多糖病（MPS）是一类遗传性疾病