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Mini-Review Article

Angelman综合征的基因治疗：当代方法和未来的努力。

卷 19, 期 6, 2019

页: [359 - 366] 页: 8

弟呕挨: 10.2174/1566523220666200107151025

价格: $65

摘要

背景：Angelman综合征（AS）是一种先天性非遗传性神经发育障碍。当代的AS管理是有症状的，基因治疗可能在AS的治疗中起关键作用。 目的：本研究的目的是总结现有的和建议的天使疗法综合症的基因治疗方法。 方法：这是一篇文献综述。研究了Pubmed和Scopus数据库中的关键字（基因治疗，安格曼综合症，神经系统疾病，新生儿）。同行评议的研究与Angelman综合征的基因疗法密切相关，并提供英语，希腊语，乌克兰语或印尼语版本。 2000年之前发表的研究被排除在外，并且与上述标准不符。 结果：UBE3A在信号传递和降解过程中起着多种作用。尽管恢复UBE3A表达而不是靶向分子的已知活性将是最佳的治疗目标，但迄今为止尚不可能。恢复父系UBE3A似乎是一个适当的选择。这可以通过施用拓扑异构酶-I抑制剂或降低UBE3A反义转录物（UBE3A-ATS）（使父系UBE3A沉默的分子）来实现。 结论：了解UBE3A印记揭示了AS病因治疗的途径。在小鼠身上测试的基因治疗模型似乎没有预期的有效，指出父系UBE3A的激活不能抵消现有的CNS缺陷。另一方面，靶向异常下游细胞信号通路已经提供了有希望的拯救作用。也许，将父本UBE3A表达的恢复与异常信号通路导向的治疗结合起来可以提供更好的治疗效果。然而，在药物经济学和伦理学背景下，AS基因疗法仍存在争议。

关键词: Angelman综合征，基因治疗，神经发育障碍，先天性，UBE3A，CNS，ATF。

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