MARROW TRANSPLANT THERAPY FOR MUCOPOLYSACCHARIDOSIS

骨髓移植是治疗某些溶酶体的一种有前途的疗法。 人类的储存障碍。捐献的白细胞可能会产生酶 持续的活动，其数量足以在正常范围内 极限。溶酶体动物的异基因骨髓移植 储存疾病将决定BMT可以预防的程度， 稳定或逆转各种溶酶体蓄积性疾病的表现。 我们建议继续使用粘多糖病VI的猫模型 (芳基硫酸酶B缺乏症)前瞻性调查 不同的临床、形态和生化表现 这种糖胺多糖储存疾病可以预防、稳定或 通过同种异体骨髓移植矫正。长期 有必要对处理过的动物进行评估，以确定底物是否 肝、软骨、角膜和其他组织减少。临床 具有许多溶酶体的动物和人的异质性是显著的。 储藏性疾病，进行疾病进展的临床评估 主观的。 建议研究更多经治疗和未治疗的骨髓移植患者。 以确定差异是否具有统计学意义。六名下院议员 VI影响-BMT处理的猫，两个MPS VI影响-BMT处理的猫 自体恢复骨髓，8个MPS VI影响非骨髓移植 治疗后的猫将继续接受监测。此外，还有6只10周大的 受MPS VI影响的猫将在第四年移植，并在第五年移植六只，用于 共有18只MPS VI感染BMT治疗的猫。额外两个MPS VI 受影响的--未经治疗的对照将从第4年开始进行监测。 在感染前和6个月后将对受影响的猫进行形态监测 每年一次的骨髓移植后，通过放射摄影、摄影、计算机体层摄影、裂隙灯 生物显微镜、视网膜电描记术、光学显微镜和电子显微镜 肝、脑、软骨、皮肤活检和尸检组织。MPS VI 猫将通过白细胞和组织芳基硫酸酯酶B进行生化监测 通过对尿液、肝脏、角膜、 软骨和耳蜗糖胺聚糖。未经治疗的猫将被监测 同样地，为了进行比较。这些研究将确定在何种程度上 具有酶活性的细胞将逆转或阻止糖胺聚糖 在受影响的靶组织中积聚和损害。来自这些的结果 研究将提供与溶酶体治疗直接相关的信息。 由骨髓移植或基因引起的人类储存障碍 心理治疗。

Bone marrow transplantation is a promising therapy for some lysosomal storage disorders in human beings. Donor leukocytes may establish enzyme activity on a continual basis in amounts sufficient to be within normal limits. Allogeneic bone marrow transplants in animals with lysosomal storage diseases will determine the degree by which BMT may prevent, stabilize, or reverse manifestations of various lysosomal storage diseases. We propose to continue to employ a feline model of mucopolysaccharidosis VI (arylsulfatase B deficiency) to investigate prospectively the degree to which various clinical, morphological, and biochemical manifestations of this glycosaminoglycan storage disease are prevented, stabilized, or corrected through allogenic bone marrow transplantation. Long term evaluation of treated animal is necessary to determine if substrate is reduced in liver, cartilage, cornea, and other tissues. Clinical heterogeneity is marked in animals and people with many of the lysosomal storage diseases, making clinical evaluation of the progression of disease subjective. It is proposed to study larger numbers of BMT treated and untreated affected animals to determine if differences are statistically significant. Six MPS VI affected-BMT treated cats, two MPS VI affected-BMT treated cats which autologously recovered their own marrow, and 8 MPS VI affected non BMT treated cats will continue to be monitored. In addition, six 10 weeks old MPS VI affected cats will be transplanted in year 4, and six in year 5, for a total of 18 MPS VI affected-BMT treated cats. Two additional MPS VI affected-non treated controls will be monitored beginning year 4. MPS VI affected cats will be monitored morphologically pre-and at 6 months then yearly post-BMT by radiography, photography, computed tomography, slit lamp biomicroscopy, electroretinography, and light and electron microscopy of liver, brain, cartilage, and skin biopsies and necropsy tissues. MPS VI cats will be monitored biochemically by leukocyte and tissue arylsulfatase B activity and by analysis and characterization of urine, liver, cornea, cartilage and cochlea glycosaminoglycans. Untreated cats will be monitored similarly for comparison. These studies will determine the degree to which enzyme-competent cells will reverse or prevent the glycosaminoglycan accumulation and lesions in affected target tissues. Results from these studies will provide information directly pertinent to therapy of lysosomal storage disorders of humans by either bone marrow transplantation or gene therapy.