Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells
Prospect for enzyme therapy in glycogenosis II variants: a study on cultured muscle cells
复制标题
糖原生成 II 变异体酶疗法的前景：培养肌肉细胞的研究
作者：
A. T. Ploeg;P. Bolhuis;R. Wolterman;J. Visser;M. Loonen;H. Busch;A. Reuser
骨骼肌功能受损是不同临床形式的糖原累积病II型的共同特征。在本研究中，使用来自不同患者的肌肉培养物来研究临床异质性的原因以及酶替代疗法的可行性。酸性α-葡萄糖苷酶的活性似乎是决定肌肉中溶酶体糖原蓄积程度的主要因素，从而决定疾病的临床严重程度。中性α-葡萄糖苷酶似乎没有影响。通过给予从人尿液中纯化的“高摄取”形式的酸性α-葡萄糖苷酶，在患者的骨骼肌培养物中实现了酶缺陷的纠正。该酶到达溶酶体，包括糖原储存泡，并且溶酶体糖原含量降低至对照水平。在正常肌细胞中，总细胞糖原库的20%被分离在溶酶体隔室中。这个百分比高于成纤维细胞，这可能部分解释了为什么肌肉更容易储存糖原。本研究的酶治疗的相关性进行了讨论。
SummaryImpairment of skeletal muscle function is the common feature of distinct clinical forms of glycogenosis type II. In the present study, muscle cultures from different patients were used to investigate the cause of clinical heterogeneity and the feasibility of enzyme replacement therapy. The activity of acid α-glucosidase appears to be the primary factor in determining the extent of lysosomal glycogen storage in muscle, and thereby the clinical severity of the disease. Neutral α-glucosidases do not seem influencial. Correction of the enzymatic defect was achieved in skeletal muscle cultures from patients by administration of a “high-uptake” form of acid α-glucosidase, purified from human urine. The enzyme reaches the lysosomes, including the glycogen storage vacuoles, and the lysosomal glycogen content is reduced to control level. In normal muscle cells 20% of the total cellular glycogen pool is segregated in lysosomal compartments. This percentage is higher than in fibroblasts, which may partly explain why muscles are more prone to store glycogen. The relevance of this study for enzyme therapy is discussed.
正常和酸性麦芽糖酶缺陷肌肉培养物的免疫细胞化学分析。
影响因子：
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作者：
Miranda,AF;Shanske,S;Hays,AP;DiMauro,S
通讯作者：
DiMauro,S