Developing new pharmacotherapeutic approaches to treating sickle-cell disease.
Developing new pharmacotherapeutic approaches to treating sickle-cell disease.
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开发新的药物治疗方法来治疗镰状细胞病。
DOI：
10.1111/voxs.12305
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Telen,MarilynJ
中科院分区：
文献类型：
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作者：
Telen,MarilynJ
SCD患者的生存期已通过支持性护理的改善而延长，包括疫苗接种、抗生素预防和包括输血在内的整体医疗管理。然而，目前只有一种获批的、部分有效的镰状细胞病药物-世界迫切需要更好的方法来治疗和预防镰状细胞病的复发性疼痛性血管闭塞发作以及终末器官损伤，这些疾病仍然无情地导致世界各地的预期寿命严重缩短。基于对镰状细胞病的异常红细胞如何导致急性疼痛发作和进行性终末器官损伤的双重祸害的积累知识，制药企业和个人研究人员现在正在寻求治疗镰状细胞病的多种新途径。因此，许多化合物正在积极开发中，包括临床前模型以及I、II和III期临床试验。这些药物靶向许多被认为在镰状细胞病中至关重要的病理生理过程，包括血红蛋白S的化学和物理行为、细胞粘附、凝血途径、血小板活化、炎症途径和血红蛋白F表达上调。此外，最近对易患某些类型的镰状细胞病相关组织损伤（如中风或肾病）的遗传变异的探索，预计将导致确定靶向这些工作所揭示的途径的药物。因此，未来5到10年有望为镰状细胞病提供新的治疗方法。
Survival for patients with SCD has been prolonged by improvements in supportive care, including vaccinations, antibiotic prophylaxis and overall medical management, including transfusion. However, there remains only one approved, partially effective drug for sickle‐cell disease—hydroxyurea (hydroxycarbamide). The world desperately needs better ways of both treating and preventing the recurrent painful vaso‐occlusive episodes pathognomonic of sickle‐cell disease as well as the end‐organ damage that still leads inexorably to severely shortened life expectancies throughout the world. Based on accumulating knowledge about how the abnormal red blood cells of sickle‐cell disease cause the double scourge of acute painful episodes and progressive end‐organ damage, both pharmaceutical enterprises and individual investigators are now pursuing multiple new avenues for treating sickle‐cell disease. As a result, many compounds are in active development, both in preclinical models as well as in phase I, II and III clinical trials. These agents target many pathophysiologic processes thought to be critical in sickle‐cell disease, including the chemical and physical behaviour of haemoglobin S, cell adhesion, coagulation pathways, platelet activation, inflammatory pathway, and upregulation of haemoglobin F expression. In addition, recent explorations of the genetic variations that predispose to certain types of sickle‐cell disease‐related tissue injury, such as stroke or nephropathy, are expected to lead to the identification of drugs targeting the pathways uncovered by such work. Thus, the next five to 10 years holds a promise of new treatments for sickle‐cell disease.