Frostegård Anna, Haegerstrand Anders
Annexin Pharmaceuticals AB, Kammakargatan 48, S-111 60 Stockholm, Sweden.
Unit of Immunology and Chronic Disease, IMM, Karolinska Institute, S-171 77 Stockholm, Sweden.
Pharmaceuticals (Basel). 2024 Jul 24;17(8):979. doi: 10.3390/ph17080979.
Despite progress in the management of patients with retinal vascular and degenerative diseases, there is still an unmet clinical need for safe and effective therapeutic options with novel mechanisms of action. Recent mechanistic insights into the pathogenesis of retinal diseases with a prominent vascular component, such as retinal vein occlusion (RVO), diabetic retinopathy (DR) and wet age-related macular degeneration (AMD), may open up new treatment paradigms that reach beyond the inhibition of vascular endothelial growth factor (VEGF). Phosphatidylserine (PS) is a novel lipid target that is linked to the pathophysiology of several human diseases, including retinal diseases. PS acts upstream of VEGF and complement signaling pathways. Annexin A5 is a protein that targets PS and inhibits PS signaling. This review explores the current understanding of the potential roles of PS as a target and Annexin A5 as a therapeutic. The clinical development status of Annexin A5 as a therapeutic and the potential utility of PS-Annexin A5 as a theranostic pairing in retinal vascular conditions in particular is described.
尽管在视网膜血管疾病和退行性疾病患者的管理方面取得了进展，但对于具有新型作用机制的安全有效的治疗选择，临床上仍有未满足的需求。最近对具有突出血管成分的视网膜疾病（如视网膜静脉阻塞（RVO）、糖尿病性视网膜病变（DR）和湿性年龄相关性黄斑变性（AMD））发病机制的机制性见解，可能会开辟超越抑制血管内皮生长因子（VEGF）的新治疗模式。磷脂酰丝氨酸（PS）是一种新型脂质靶点，与包括视网膜疾病在内的几种人类疾病的病理生理学有关。PS在VEGF和补体信号通路的上游起作用。膜联蛋白A5是一种靶向PS并抑制PS信号传导的蛋白质。本综述探讨了目前对PS作为靶点以及膜联蛋白A5作为治疗剂的潜在作用的理解。描述了膜联蛋白A5作为治疗剂的临床开发状况，特别是PS-膜联蛋白A5作为视网膜血管疾病中治疗诊断配对的潜在效用。
