培加他汀用于湿性黄斑变性。

Pegaptanib for wet macular degeneration.

作者信息

Fraunfelder Frederick W

机构信息

National Registry of Drug-Induced Ocular Side Effects, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon 97239-4197, USA.

出版信息

Drugs Today (Barc). 2005 Nov;41(11):703-9. doi: 10.1358/dot.2005.41.11.917340.

Abstract

Pegaptanib sodium injection (Macugen, Eyetech Pharmaceuticals, Pfizer, New York, NY, USA) is a relatively new medication intended to treat the so-called wet (neovascular ) form of age-related macular degeneration (AMD). This form of AMD is characterized by the growth of unwanted new blood vessels into the macula (angiogenesis). The aqueous solution containing pegaptanib is injected into the vitreous of the eye, where it binds to the 165 amino acid isoform of vascular endothelial growth factor (VEGF), a secreted protein that is thought to play a major role in the pathologic angiogenesis that occurs in wet AMD. Neovascular AMD is the leading cause of severe vision loss in people over age 60 in the United States and other industrialized countries (1). Pegaptanib acts as a selective VEGF antagonist through its molecular structure as an aptamer, a pegylated modified oligonucleotide that adopts a three-dimensional configuration, enabling it to bind to extracellular VEGF (Fig. 1). Aptamers are macromolecules composed of chemically synthesized single-stranded nucleic acids (either RNA or DNA) that bind with a high degree of selectivity and affinity when exposed to target proteins. Pegaptanib binds VEGF165, and bound VEGF165 is not able to bind to the VEGF receptor, thereby negating its ability to cause angiogenesis and vascular permeability. Other aptamers exist, as do other forms of treatment for AMD. To date, however, no treatment for AMD has allowed for better vision after treatment, with most surgical treatments leading to almost immediate loss of some vision in the expectation of preventing more severe loss. Research in the field of macular degeneration is advancing rapidly, and treatment with an aptamer such as pegaptanib is a viable option despite the possibility of adverse events.

摘要

pegaptanib钠注射液(Macugen,美国纽约辉瑞公司旗下的Eyetech制药公司生产)是一种相对较新的药物,用于治疗所谓的湿性(新生血管性)年龄相关性黄斑变性(AMD)。这种形式的AMD的特征是黄斑区出现不需要的新生血管生长(血管生成)。含有pegaptanib的水溶液被注射到眼玻璃体内,在那里它与血管内皮生长因子(VEGF)的165个氨基酸异构体结合,VEGF是一种分泌蛋白,被认为在湿性AMD中发生的病理性血管生成中起主要作用。新生血管性AMD是美国和其他工业化国家60岁以上人群严重视力丧失的主要原因(1)。pegaptanib作为一种适体,通过其分子结构作为选择性VEGF拮抗剂发挥作用,适体是一种聚乙二醇化修饰的寡核苷酸,具有三维构型,使其能够与细胞外VEGF结合(图1)。适体是由化学合成的单链核酸(RNA或DNA)组成的大分子,当暴露于靶蛋白时,它们以高度的选择性和亲和力结合。pegaptanib与VEGF165结合,结合的VEGF165不能与VEGF受体结合,从而消除其引起血管生成和血管通透性的能力。其他适体以及AMD的其他治疗形式也存在。然而,迄今为止,没有一种AMD治疗方法能在治疗后带来更好的视力,大多数手术治疗在期望预防更严重视力丧失的情况下几乎会立即导致部分视力丧失。黄斑变性领域的研究正在迅速发展,尽管可能会出现不良事件,但使用pegaptanib等适体进行治疗是一种可行的选择。

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