Drug Discovery Today ( IF 6.5 ) Pub Date : 2021-07-24 , DOI: 10.1016/j.drudis.2021.07.015 Marie Cadé 1 , Javier Muñoz-Garcia 1 , Antoine Babuty 2 , Marc Fouassier 3 , Marie-Francoise Heymann 1 , Paul E Monahan 4 , Dominique Heymann 5
Hemophilia A is an X-linked hereditary disorder that results from deficient coagulation factor VIII (FVIII) activity, leading to spontaneous bleeding episodes, particularly in joints and muscles. FVIII deficiency has been associated with altered bone remodeling, dysregulated macrophage polarization, and inflammatory processes that are associated with the neoformation of abnormal blood vessels. Treatment based on FVIII replacement can lead to the development of inhibitors that render FVIII concentrate infusion ineffective. In this context, hemophilia has entered a new therapeutic era with the development of new drugs, such as emicizumab, that seek to restore the hemostatic balance by bypassing pathologically acquired antibodies. We discuss the potential extrahemostatic functions of FVIII that may be crucial for defining future therapies in hemophilia.
中文翻译:
FVIII 处于凝血、骨骼和免疫生物学的十字路口:止血之外生物活性的新证据
血友病 A 是一种 X 连锁遗传性疾病,由凝血因子 VIII (FVIII) 活性不足引起,导致自发性出血,特别是在关节和肌肉中。FVIII 缺乏与骨重塑改变、巨噬细胞极化失调和与异常血管新生相关的炎症过程有关。基于 FVIII 替代的治疗可能导致抑制剂的发展,使 FVIII 浓缩输注无效。在此背景下,随着新药的开发,血友病进入了一个新的治疗时代,例如 emicizumab,旨在通过绕过病理获得性抗体来恢复止血平衡。