In this last decade, a deeper understanding of the pathophysiology of hereditary red cell disorders and the development of novel classes of pharmacologic agents have provided novel therapeutic approaches to thalassemias, sickle cell disease (SCD), and other red cell disorders. Here, we analyze and discuss the novel therapeutic options according to their targets, taking into consideration the complex process of erythroid differentiation, maturation, and survival of erythrocytes in the peripheral circulation. We focus on active clinical exploratory and confirmatory trials on thalassemias, SCD, and other red cell disorders. Beside β-thalassemia and SCD, we found that the development of new therapeutic strategies has allowed for the design of clinic studies for hereditary red cell disorders still lacking valuable therapeutic alternative such as α-thalassemias, congenital dyserythropoietic anemia, or Diamond-Blackfan anemia. In addition, reduction of heme synthesis, which can be achieved by the repurposed antipsychotic drug bitopertin, might affect not only hematological disorders but multiorgan diseases such as erythropoietic protoporphyria. Finally, our review highlights the current state of therapeutic scenarios, in which multiple indications targeting different red cell disorders are being considered for a single agent. This is a welcome change that will hopefully expand therapeutic option for patients affected by thalassemias, SCD, and other red cell disorders.

中文翻译：

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地中海贫血、镰状细胞病和其他红细胞疾病的新治疗方法


在过去的十年中，对遗传性红细胞疾病病理生理学的深入了解以及新型药物制剂的开发为地中海贫血、镰状细胞病 (SCD) 和其他红细胞疾病提供了新的治疗方法。在这里，我们根据其靶标分析和讨论新的治疗方案，同时考虑到外周循环中红细胞分化、成熟和存活的复杂过程。我们专注于地中海贫血、SCD 和其他红细胞疾病的积极临床探索性和验证性试验。除了 β 地中海贫血和 SCD 之外，我们发现新的治疗策略的开发已经允许设计针对仍缺乏有价值的治疗替代方案的遗传性红细胞疾病的临床研究，例如 α 地中海贫血、先天性红细胞生成障碍性贫血或 Diamond-Blackfan 贫血。此外，通过重新利用抗精神病药物比托汀可以减少血红素合成，这可能不仅会影响血液系统疾病，还会影响多器官疾病，例如红细胞生成性原卟啉症。最后，我们的综述强调了治疗方案的当前状态，其中正在考虑使用单一药物针对不同红细胞疾病的多种适应症。这是一个值得欢迎的变化，有望扩大地中海贫血、SCD 和其他红细胞疾病患者的治疗选择。