Erratum: Intracranial injection of recombinant adeno-associated virus improves cognitive function in a murine model of mucopolysaccharidosis type VII (Molecular Therapy (2001) vol. 3 (3) (351-358))
Erratum: Intracranial injection of recombinant adeno-associated virus improves cognitive function in a murine model of mucopolysaccharidosis type VII (Molecular Therapy (2001) vol. 3 (3) (351-358))
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勘误表：颅内注射重组腺相关病毒可改善 VII 型粘多糖贮积症小鼠模型的认知功能（Molecular Therapy (2001) vol. 3 (3) (351-358)）
DOI：
10.1006/mthe.2001.0349
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发表时间：
2001
影响因子：
12.4
通讯作者：
M. Sands
中科院分区：
文献类型：
--
作者：
W. Frisella;L. O'Connor;C. Vogler;M. Roberts;S. Walkley;B. Levy;T. Daly;M. Sands
粘多糖沉积症VII型（MPS VII）是一种由β-葡萄糖醛酸酶（GUSB）活性缺乏引起的溶酶体贮积病。GUSB缺乏导致未降解的糖胺聚糖（GAG）在包括脑在内的大多数组织的细胞中进行性积累，并且与智力迟钝相关。减少中枢神经系统中的溶酶体蓄积和预防认知功能障碍可能需要在新生儿期间颅内递送治疗剂，其提供GUSB的连续来源。因此，我们将编码人GUSB的重组腺相关病毒注射到新生MPS VII小鼠的前皮质和海马中。到18周时，大脑中的总GUSB活动接近正常水平。虽然GUSB活性集中在注射部位附近，但在大脑的大部分区域中溶酶体扩张减少。除了GAG减少的组织病理学证据外，还防止了先前未描述的GM 2和GM 3神经节苷脂在脑中的蓄积。此外，GUSB表达和溶酶体扩张减少与Morris水迷宫试验中测量的认知功能改善相关。这些发现表明，GUSB的局部过表达对病理和认知功能具有积极影响，并且没有明显的毒性。
Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by the lack of β-glucuronidase (GUSB) activity. GUSB deficiency leads to the progressive accumulation of undegraded glycosaminoglycans (GAGs) in cells of most tissues, including the brain, and is associated with mental retardation. Reduction of lysosomal storage in the central nervous system and prevention of cognitive dysfunction may require intracranial delivery of a therapeutic agent during the newborn period that provides a continuous source of GUSB. Therefore, we injected recombinant adeno-associated virus encoding human GUSB into both the anterior cortex and the hippocampus of newborn MPS VII mice. Total GUSB activity in the brain approached normal levels by 18 weeks. Although GUSB activity was concentrated near the injection sites, lysosomal distension was reduced in most areas of the brain. In addition to histopathologic evidence of GAG reduction, the previously undescribed accumulation of GM2 and GM3 gangliosides in the brain was also prevented. Furthermore, GUSB expression and reduced lysosomal distension correlated with improvements in cognitive function as measured in the Morris Water Maze test. These findings indicate that localized overexpression of GUSB has positive effects on the pathology and cognitive function and does not have overt toxicity.