STUDIES ON THE MECHANISM OF PATHOGENESIS OF THE MUCOPOLYSACCHARIDOSES

点击翻译按钮获取中文摘要

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.