STUDIES ON THE MECHANISM OF PATHOGENESIS OF THE MUCOPOLYSACCHARIDOSES

粘多糖病(MPS)是一组遗传性疾病 以糖胺多聚糖(GAG)代谢缺陷为特征。这个 精神障碍通常与严重的神经功能障碍有关。 系统以及肝、脾、心脏、骨骼和其他组织。 本课题的主要目的是研究黄斑狼疮的发病机制。 这些疾病的重点是大脑受累和智力低下。 我们正在使用一种比较的方法。为此，我们研究了 组织中GAG、鞘脂和相关溶酶体酶的变化 不同类型的MPS患者，我们在以下方面进行了关联 临床和超微结构表现。我们的实验室贡献了 对理解化学病理学，特别是对 MPS IH、MPS IS、MPS II、MPS III A和MPS III B的神经化学。 补充人类受试者的研究，一种药物(苏拉明)诱导的动物 建立了MPS动物模型，建立了MPS犬模型(Natural) (α-L-艾杜糖醛酸酶缺乏症)，已有充分的特征。在一个 试图扭转这种不治之症造成的渐进性恶化 代谢紊乱，5只患有MPS I的狗被移植了来自 正常或杂合的产仔数。移植的骨髓提供了 受影响的狗有产生这种酶的细胞的自我更新来源 来完成新陈代谢过程。移植后一年 对于这种神经退行性代谢来说，结果是非常令人鼓舞的 无序是因为我们在中枢神经系统中发现了明显的矫正变化 狗的神经系统。

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 I 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.