Van der Ploeg A T, Loonen M C, Bolhuis P A, Busch H M, Reuser A J, Galjaard H
Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
Pediatr Res. 1988 Jul;24(1):90-4. doi: 10.1203/00006450-198807000-00021.
Attempts at treatment of glycogenosis type II and other lysosomal storage disorders by enzyme replacement have been reported. Parenteral enzyme administration has been ineffectual. Treatment by bone marrow transplantation is currently under investigation. We have used cultured skeletal muscle cells from a patient with infantile glycogenosis type II to study fundamental aspects of enzyme replacement therapy. Efficient uptake of acid alpha-glucosidase was achieved by using the mannose-6-phosphate receptor on the cell surface as a target for an enzyme precursor with phosphorylated high-mannose types carbohydrate chains purified from human urine. We found that the enzyme was channeled to the lysosomes and converted to mature acid alpha-glucosidase. Glycogen storage was reversed. The results are discussed in relation to treatment of glycogenosis type II.
据报道，已经尝试通过酶替代疗法治疗II型糖原贮积病和其他溶酶体贮积症。肠胃外给予酶一直无效。目前正在研究通过骨髓移植进行治疗。我们使用来自一名II型婴儿糖原贮积病患者的培养骨骼肌细胞来研究酶替代疗法的基本方面。通过将细胞表面的甘露糖-6-磷酸受体作为从人尿中纯化的具有磷酸化高甘露糖型碳水化合物链的酶前体的靶标，实现了酸性α-葡萄糖苷酶的有效摄取。我们发现该酶被引导至溶酶体并转化为成熟的酸性α-葡萄糖苷酶。糖原蓄积得到逆转。结合II型糖原贮积病的治疗对结果进行了讨论。
