Suppr超能文献

重新利用富马酸二甲酯靶向Nrf2以减缓地图样萎缩区域的生长。

Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy.

作者信息

Camelo Serge

机构信息

Independent Researcher, 193 Avenue du Président Wilson, 93210 Saint-Denis, France.

出版信息

Int J Mol Sci. 2025 Jun 25;26(13):6112. doi: 10.3390/ijms26136112.

Abstract

Recently, marketing authorizations were granted by the Federal Drug Administration (FDA) for pegcetacoplan and avacincaptad pegol, which inhibit C3 and C5 complement components, respectively. These two drugs were demonstrated to slow down the growth of atrophic areas in the retina. These authorizations represent a huge breakthrough for patients suffering from geographic atrophy (GA), the late stage of the dry form of Age-related Macular Degeneration (AMD). Until then, no treatment was available to treat this blinding disease. However, these two new compounds inhibiting the complement system are still not available for patients outside of the United States, and they are not devoid of drawbacks, including a poor effect on vision improvement, an increased risk of occurrence of the neovascular form of AMD and the burden of patients receiving recurrent intravitreal injections. Thus, the important medical need posed by GA remains incompletely answered, and new therapeutic options with alternative modes of action are still required. Oxidative stress and inflammation are two major potential targets to limit the progression of atrophic retinal lesions. Dimethyl fumarate, dimethyl itaconate and other activators of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) display antioxidants and immunomodulatory properties that have shown evidence of efficacy in in vitro and in vivo models of dry AMD. Tecfidera, whose active principle is dimethyl fumarate, is already commercialized for the treatment of autoimmune diseases such as multiple sclerosis and psoriasis. The aim of this review is to present the rationale and the design of the clinical trial we initiated to test the effectiveness and safety of repurposing Tecfidera, which could represent a new therapeutic alternative in patients with the dry form of AMD.

摘要

最近,美国食品药品监督管理局(FDA)批准了聚乙二醇化醋氨己酸和阿伐西普他德聚乙二醇的上市许可,它们分别抑制补体成分C3和C5。这两种药物已被证明可减缓视网膜萎缩区域的生长。这些批准对于患有地图样萎缩(GA)的患者而言是一项重大突破,GA是干性年龄相关性黄斑变性(AMD)的晚期阶段。在此之前,尚无治疗这种致盲疾病的方法。然而,这两种抑制补体系统的新化合物在美国境外的患者中仍无法使用,并且它们并非没有缺点,包括对视力改善效果不佳、新生血管性AMD发生风险增加以及患者接受反复玻璃体内注射的负担。因此,GA所带来的重大医疗需求仍未得到充分满足,仍需要具有替代作用方式的新治疗选择。氧化应激和炎症是限制萎缩性视网膜病变进展的两个主要潜在靶点。富马酸二甲酯、衣康酸二甲酯和其他转录因子核因子红细胞2相关因子2(Nrf2)激活剂具有抗氧化和免疫调节特性,已在干性AMD的体外和体内模型中显示出疗效证据。活性成分是富马酸二甲酯的特立氟胺已被商业化用于治疗自身免疫性疾病,如多发性硬化症和牛皮癣。本综述的目的是介绍我们启动的一项临床试验的基本原理和设计,以测试重新利用特立氟胺的有效性和安全性,这可能为干性AMD患者提供一种新的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c60/12249891/bca9c904e242/ijms-26-06112-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验