STUDIES ON 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。 这些障碍通常与严重的 神经系统以及肝、脾、心、骨等 纸巾。本课题的目标是研究黄曲霉毒素的作用机制。 这些疾病的发病机制以脑受累为重点 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GAG、鞘脂和 不同疾病患者组织中相关溶酶体酶的研究 MPS的类型，我们从临床和临床角度进行相关分析 超微结构的发现。我们的实验室做出了重大贡献 了解化学病理学，特别是 MPS IH、MPS IS、MPS II、MPS III A和MPS III B的神经化学。 为了补充人体研究，一种药物(苏拉明) 建立了诱导性MPS动物模型，建立了犬MPS动物模型，建立了MPS动物模型。 (自然)，MPS I(α-L艾杜糖酸酶缺乏症)，已 完全有特点的。试图扭转进步的趋势 由这种无法治愈的代谢紊乱引起的恶化，五 将患有MPS I的狗的骨髓移植到正常或 杂合子产仔。移植的骨髓提供了 受影响的狗有自我更新的细胞来源，产生 完成代谢过程所需的酶。其中的两个 受者在骨髓移植(BMT)后死亡 第628天和第594天，当时两人都是临床健康的。大型 从包括大脑在内的所有组织中减少储存的呕吐， 这似乎是BMT治疗犬MPS的一致结果 我。

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 doges 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. Two of these recipients were killed on post-bone marrow transplantation (BMT) day 628 and 594 at which time both were clinically healthy. Large reduction of stored GAGs, from all tissues including the brain, appears to be consistent consequence of BMT therapy in canine MPS I.