El-Beshlawy Amal, El-Ghamrawy Mona
Pediatric Hematology & BMT Unit, Pediatrics Department, Cairo University, Cairo, Egypt.
Pediatric Hematology & BMT Unit, Pediatrics Department, Cairo University, Cairo, Egypt.
Blood Cells Mol Dis. 2019 May;76:53-58. doi: 10.1016/j.bcmd.2019.01.006. Epub 2019 Feb 4.
Thalassemia is a common inherited monogenic disease. It is characterized by chronic hemolysis, ineffective erythropoiesis (IE) and iron overload. Despite advances in transfusion practices and chelation therapy, still many limitations in delivering these standard therapies exist. Challenges of currently available standard care and advances in understanding the underlying pathophysiological mechanisms in thalassemia stimulated research towards development of novel therapeutic targets. Agents reducing IE as Jak 2 inhibitors and Activin II receptor traps are promising and are currently in clinical trials. Other approaches targeting iron dysregulation as mini-hepcidins, exogenous transferrin and erythroferrone inhibitors are in preclinical studies. Gene therapy, a rapidly evolving field, has exhibited remarkable progress in recent years. Studies have focused on β or γ-globin addition, over expression of endogenous γ-globin-activating transcription factors, silencing of γ-globin repressors and genome editing of β-globin mutations or γ-globin repressors. In this article we provide an overview of emerging recent trends in treatment of thalassemia targeting IE, iron dysregulation and novel curative treatments as gene therapy and gene editing.
地中海贫血是一种常见的遗传性单基因疾病。其特征为慢性溶血、无效红细胞生成（IE）和铁过载。尽管输血治疗和螯合疗法取得了进展，但在提供这些标准疗法方面仍存在许多限制。当前可用标准治疗的挑战以及在地中海贫血潜在病理生理机制认识上的进展，激发了针对新型治疗靶点研发的研究。如 Jak 2 抑制剂和激活素 II 受体陷阱等减少 IE 的药物很有前景，目前正处于临床试验阶段。其他针对铁代谢失调的方法，如微型铁调素、外源性转铁蛋白和促红细胞生成素抑制剂，正处于临床前研究阶段。基因治疗是一个快速发展的领域，近年来已取得显著进展。研究除了聚焦于β或γ珠蛋白外，还包括内源性γ珠蛋白激活转录因子的过表达、γ珠蛋白抑制因子的沉默以及β珠蛋白突变或γ珠蛋白抑制因子的基因组编辑。在本文中，我们概述了地中海贫血治疗中针对 IE、铁代谢失调以及作为基因治疗和基因编辑的新型治愈性治疗方法的最新趋势。
