STUDIES ON THE MUCOPOLYSACCHARIDOSES

粘多糖病(MPS)是一组遗传性 以人体新陈代谢缺陷为特征的疾病 糖胺聚糖(GAG)。这些障碍通常与 神经系统和肝脏都有严重的功能障碍， 脾、心脏、骨骼和其他组织。该项目的目标是 对这些疾病发病机制的研究 强调大脑参与和精神发育迟缓。我们是 使用比较的方法。为此，我们研究了 GAG、鞘脂和相关溶酶体酶的变化 在各种类型的MPS患者的组织中，我们制作了 在临床和超微结构方面的相关性。我们的 实验室在了解这种化学物质方面做出了重大贡献 MPS的病理，特别是神经化学 是、第二阶段计划、第三阶段计划A及第三阶段计划B，以补充研究 在人类受试者中，一种药物(苏拉明)诱导的动物模型 MPS已被开发出来，并建立了MPS的犬模型(自然) (α-L-艾杜糖醛酸酶缺乏症)，已有充分的特征。在……里面 试图扭转由此导致的逐渐恶化的局面 无法治愈的代谢紊乱，5只患有MPS 1的狗被 用正常或杂合子骨髓移植 一窝产仔。移植的骨髓提供了受影响的 具有自我更新来源的细胞产生这种酶的狗 来完成新陈代谢过程。一年后 移植的结果是非常令人鼓舞的。 神经退行性代谢紊乱是因为我们发现 狗的中枢神经系统内的矫正变化。

The mucopolysaccharidoses (MPS) are a group of hereditary diseases characterized by defective metabolism of glycosaminoglycans (GAGs). 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 GAGs, 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, MPS II, MPS III A and MPS III B. To complement the studies with human subjects, a drug (suramin) induced animal model of MPS has been developed and a canine model, (natural), of MPS I (alpha-L-iduronidase deficiency), has been fully characterized. In an attempt to reverse the progressive deterioration caused by this incurable metabolic disorder, five dogs with MPS 1 were transplanted with marrow from normal or heterozygous littermates. Transplanted bone marrow provides the affected dogs with self-renewing source of cells that produce the enzyme needed to complete the metabolic process. One year after transplantation the results are very encouraging for this neurodegenerative metabolic disorder because we found marked corrective changes within the central nervous system of the dogs.