Department of Hematology and Medical Oncology, Centre Universitaire de l'Université de Montréal (CHUM), Montreal, Quebec, Canada.
Expert Opin Emerg Drugs. 2022 Jun;27(2):211-224. doi: 10.1080/14728214.2022.2105835. Epub 2022 Aug 1.
The substitution of glutamic acid by valine on the ß-globin chain produces the hemoglobin S variant responsible for sickle cell disease (SCD), a disorder that affects millions of people worldwide and leads to acute and cumulative organ damage. Even though life expectancy has significantly improved where the best medical care is available, there are still few therapeutic options for SCD and those are limited by their availability, cost, and individual toxicities.
This review summarizes the clinical data on current treatments for SCD and emerging therapies studied in the acute setting as well as potential disease-modifying agents, with an emphasis on the FDA-approved agents.
Hydroxyurea has been a gold standard for two decades, showing benefits in acute complications and overall survival in sickle cell anemia, although data is lacking for certain genotypes such as hemoglobin SC. As progress is made in our understanding of the pathophysiological networks characterizing SCD, numerous pathways appear to be targetable, with L-glutamine, crizanlizumab and voxelotor now approved by the FDA. Pursuing a multi-agent approach could alter the disease course in a more effective fashion and provide an alternative option to curative therapies, but longer clinical studies are needed.
β-珠蛋白链上的谷氨酸被缬氨酸取代会产生血红蛋白 S 变体，该变体负责镰状细胞病（SCD），这是一种影响全球数百万人的疾病，并导致急性和累积性器官损伤。尽管在提供最佳医疗护理的地方，患者的预期寿命已经显著提高，但 SCD 的治疗选择仍然很少，而且这些选择受到可用性、成本和个体毒性的限制。
本综述总结了 SCD 目前治疗方法的临床数据以及急性治疗中研究的新兴疗法，以及潜在的疾病修饰剂，重点是 FDA 批准的药物。
羟基脲作为 20 年来的金标准，在镰状细胞性贫血的急性并发症和总体生存方面显示出益处，尽管缺乏某些基因型（如血红蛋白 SC）的数据。随着我们对 SCD 特征性病理生理网络的理解不断取得进展，许多途径似乎都可以成为靶向治疗的目标，L-谷氨酰胺、crizanlizumab 和 voxelotor 现已获得 FDA 批准。采用多药物治疗方法可能会以更有效的方式改变疾病进程，并提供一种替代根治性治疗的选择，但还需要进行更长时间的临床研究。
