van Dijk Myrthe J, de Wilde Jonathan R A, Bartels Marije, Kuo Kevin H M, Glenthøj Andreas, Rab Minke A E, van Beers Eduard J, van Wijk Richard
Department of Central Diagnostic Laboratory - Research, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Center for Benign Hematology, Thrombosis and Hemostasis - Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, the Netherlands.
Department of Central Diagnostic Laboratory - Research, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Blood Rev. 2023 Sep;61:101103. doi: 10.1016/j.blre.2023.101103. Epub 2023 Jun 12.
Novel developments in therapies for various hereditary hemolytic anemias reflect the pivotal role of pyruvate kinase (PK), a key enzyme of glycolysis, in red blood cell (RBC) health. Without PK catalyzing one of the final steps of the Embden-Meyerhof pathway, there is no net yield of adenosine triphosphate (ATP) during glycolysis, the sole source of energy production required for proper RBC function and survival. In hereditary hemolytic anemias, RBC health is compromised and therefore lifespan is shortened. Although our knowledge on glycolysis in general and PK function in particular is solid, recent advances in genetic, molecular, biochemical, and metabolic aspects of hereditary anemias have improved our understanding of these diseases. These advances provide a rationale for targeting PK as therapeutic option in hereditary hemolytic anemias other than PK deficiency. This review summarizes the knowledge, rationale, (pre)clinical trials, and future advances of PK activators for this important group of rare diseases.
各种遗传性溶血性贫血治疗方法的新进展反映了丙酮酸激酶（PK）这一糖酵解关键酶在红细胞（RBC）健康中的关键作用。没有PK催化糖酵解途径（Embden-Meyerhof途径）的最后步骤之一，糖酵解过程中就没有三磷酸腺苷（ATP）的净产量，而糖酵解是红细胞正常功能和存活所需能量产生的唯一来源。在遗传性溶血性贫血中，红细胞健康受到损害，因此寿命缩短。尽管我们对一般糖酵解，尤其是PK功能的了解很扎实，但遗传性贫血在遗传、分子、生化和代谢方面的最新进展增进了我们对这些疾病的理解。这些进展为将PK作为除PK缺乏症之外的遗传性溶血性贫血的治疗选择提供了理论依据。本综述总结了针对这一重要罕见病群体的PK激活剂的知识、理论依据、（前）临床试验及未来进展。
