Using the past to inform the future: anti-VEGF therapy as a road map to develop novel therapies for diabetic retinopathy.
Using the past to inform the future: anti-VEGF therapy as a road map to develop novel therapies for diabetic retinopathy.
复制标题
DOI：
10.2337/db12-1744
复制
发表时间：
2013-06
期刊：
影响因子：
7.7
通讯作者：
Antonetti DA
中科院分区：
文献类型：
--
作者：
Titchenell PM;Antonetti DA
针对血管内皮生长因子 (VEGF) 的治疗正在彻底改变糖尿病视网膜病变 (DR) 和糖尿病黄斑水肿 (DME) 的治疗。 2012 年 8 月，雷珠单抗（一种专为眼部使用而设计的针对 VEGF 的单克隆抗体片段）成为第一个也是唯一一个获得美国食品和药物管理局批准的 DME 药物治疗方法，也是 25 年来第一个获得批准的治疗方法。此次批准基于强有力的临床前数据，随后进行了大量临床试验，这些临床试验证明 VEGF 在正常生理学和疾病病理学中的血管通透性和血管生成中发挥着重要作用。在本视角中，我们将研究有助于成功开发针对 VEGF 的疗法的实验研究和科学数据，并考虑这些方法如何为未来糖尿病眼病疗法的开发提供信息。基于既定的药物开发原则，提出了多点模型，旨在提高临床药物开发的成功率。该模型表明，为了提供经过验证的临床前靶标，研究人员应证明以下内容：靶标在正常生理学中的作用、与疾病发病机制的因果关系、与人类疾病的相关性，以及通过多种化学多样化干预措施在动物模型中引发疾病表型的临床相关改善的能力。该模型将提供一个框架来验证当前的临床前目标并确定新的目标以提高 DR 药物开发的成功率。
Therapies targeting vascular endothelial growth factor (VEGF) are revolutionizing the treatment of diabetic retinopathy (DR) and diabetic macular edema (DME). In August 2012, ranibizumab, a monoclonal antibody fragment targeting VEGF designed for ocular use, became the first and only U.S. Food and Drug Administration–approved medical therapy for DME and the first approved treatment in over 25 years. This approval was based on strong preclinical data followed by numerous clinical trials that demonstrate an essential role of VEGF in vascular permeability and angiogenesis in both normal physiology and disease pathology. In this Perspective, we will examine the experimental studies and scientific data that aided in the success of the development of therapies targeting VEGF and consider how these approaches may inform the development of future therapeutics for diabetic eye disease. A multipoint model is proposed, based on well-established drug development principles, with the goal of improving the success of clinical drug development. This model suggests that to provide a validated preclinical target, investigators should demonstrate the following: the role of the target in normal physiology, a causal link to disease pathogenesis, correlation to human disease, and the ability to elicit clinically relevant improvements of disease phenotypes in animal models with multiple, chemically diverse interventions. This model will provide a framework to validate the current preclinical targets and identify novel targets to improve drug development success for DR.
登录
查看更多内容
影响因子：
3.9
作者：
Demircan, N.;Safran, B. G.;Sizmaz, S.
通讯作者：
Sizmaz, S.
影响因子：
13.7
作者：
Abraham, Prema;Adelman, Ron A.;Zhi, Xin (Eric)
通讯作者：
Zhi, Xin (Eric)
影响因子：
13.7
作者：
Cunningham, ET Jr;Adamis, AP;Schwartz, SD
通讯作者：
Schwartz, SD
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
影响因子：
--
作者：
Adamis, AP;Shima, DT;Miller, JW
通讯作者：
Miller, JW