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Review Article

β地中海贫血的基因治疗和其他靶向治疗方法的最新进展

卷 20, 期 16, 2019

页: [1603 - 1623] 页: 21

弟呕挨: 10.2174/1389450120666190726155733

价格: $65

摘要

β地中海贫血是一种遗传性疾病，其特征是成年血红蛋白的β珠蛋白链合成受损。该疾病具有影响多个器官系统的复杂病理生理学。 β地中海贫血的主要并发症是无效的红细胞生成，慢性溶血性贫血和含铁血黄素引起的器官功能障碍。定期输血是重度β地中海贫血的主要治疗方法；但是，这种治疗可能会导致心脏和肝脏含铁血黄素沉着症-这些患者最常见的死亡原因。这篇综述的重点是针对地中海贫血的独特的未来治疗性干预措施，可以逆转脾肿大，减少输血频率，降低器官中的铁毒性以及纠正慢性贫血。有针对性的有效方案包括血红蛋白胎儿诱导剂，无效的红细胞生成纠正剂，抗氧化剂，维生素和天然产物。白藜芦醇是一种新的草药治疗方法，可作为β地中海贫血的胎儿血红蛋白诱导剂。造血干细胞移植（HSCT）是治疗重型β地中海贫血的唯一疗法，与铁螯合和输血相比，造血干细胞移植更可确保这些患者的长寿。同时，已经出现了几种分子疗法，例如ActRIIB / IgG1 Fc重组蛋白，以解决β地中海贫血的并发症或现有药物的不良反应。关于基因校正策略，一项名为HGB-207（Northstar-2; NCT02906202）的III期临床试验正在评估LentiGlobin自体细胞移植的有效性和安全性。先进的基因编辑方法旨在在婴儿期切割目标位点的DNA并将HbF转换为HbA，例如抑制BCL11A（B细胞淋巴瘤11A），HPFH（胎儿血红蛋白的遗传性持久性）和锌指核酸酶。基因疗法发展迅速，许多国家都在进行多项临床试验，并且有望在不久的将来提供商业产品。

关键词: 地中海贫血，基因疗法，铁螯合疗法，HbF诱导剂，分子疗法，地中海贫血并发症。

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图形摘要

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