STUDIES ON THE MUCOPOLYSACCHARIDOSES

粘多糖沉积症（MPS）是一组遗传性 以代谢缺陷为特征的疾病 糖胺聚糖（GAG）。 这些疾病通常与 伴有严重的神经系统和肝脏功能障碍， 脾脏心脏骨骼和其他组织 本项目的目标是 研究这些疾病的发病机制， 强调大脑参与和智力迟钝。 我们 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 在不同类型MPS患者的组织中， 在临床和超微结构方面的相关性。 我们 实验室在理解化学物质方面做出了重大贡献 病理学，特别是MPS IH，MPS IS、MPS II、MPS III A和MPS III B。 为了补充研究， 用人类受试者，药物（苏拉明）诱导的动物模型， 已经开发了MPS和MPS I的犬模型（自然） （α-L-艾杜糖醛酸酶缺乏症）已得到充分表征。 在 试图扭转由此造成的逐步恶化， 无法治愈的代谢紊乱，五只MPS 1的狗被 移植来自正常或杂合子的骨髓 同窝出生的 移植的骨髓为受影响的人 具有自我更新细胞来源的狗， 完成代谢过程所需的能量 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，因为我们发现 狗中枢神经系统内的纠正变化。

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.