Recycled Translation: Repurposing Drugs for Stroke.
Recycled Translation: Repurposing Drugs for Stroke.
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DOI：
10.1007/s12975-022-01000-z
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发表时间：
2022-12
影响因子：
6.9
通讯作者：
Hess, David C.
中科院分区：
文献类型：
--
作者：
Spellicy, Samantha E.;Hess, David C.
中风仍然是世界范围内死亡和长期残疾的主要原因，经常被描述为临床墓地。虽然多种小分子疗法已经在中风中进行了临床试验，但目前只有一种美国食品和药物管理局（FDA）批准的治疗中风的药物，即生物重组组织型纤溶酶原激活剂（rt-PA）。重新利用先前获得FDA批准的替代适应症的治疗方法可作为卒中治疗翻译的前瞻性选择。与新药物开发相比，再利用策略具有以患者为中心和经济优势。这包括提高安全性，增加批准的机会，减少批准的时间，减少资本投资。目前，37个活跃的脑卒中临床试验采用不同的初始适应症和剂量模式的重新定位治疗方法。目前研究的再用途疗法可分为六个机制类别：(1)抗凝；(2)血管完整性、反应或红细胞（RBC）改变；(3)免疫系统调节；(4)神经传递;(5)神经保护。利用药物数据库、硅药物-蛋白质相互作用模型、基因组数据和共识方法进行定向假设驱动的计算研究，可以确定当前的机制再利用类别是否有最高的转化成功机会，或者是否应该探索其他机制途径。随着人们越来越关注重新定位的治疗策略而不是从头开始的策略，监管保护的进化和优化需要激励创新者和研究者。
Stroke, which continues to be a leading cause of death and long-term disability worldwide, has often been described as a clinical graveyard. While multiple small molecule therapeutics have undergone clinical trials in stroke, currently only one Food and Drug Administration (FDA)-approved medication exists for the treatment of stroke, the biological, recombinant tissue plasminogen activator (rt-PA). Repurposing of therapeutics which have previously gained FDA approval for alternative indications serves as a prospective option for stroke therapeutic translation. In contrast to de novo drug development, repurposing strategies have patient-centered and economic advantages. These include increased safety, increased chance of approval, decreased time to approval, and decreased capital investment. Presently, 37 active stroke clinical trials utilize repurposed therapeutics with various initial indications and dosing paradigms. The currently studied repurposed therapeutics fall into six mechanistic categories: (1) anticoagulation; (2) vasculature integrity, response, or red blood cell (RBC) alterations; (3) immune system regulation; (4) neurotransmission; and (5) neuroprotection. Directed hypothesis-driven computational investigation utilizing drug databases, in silico drug-protein interaction modeling, genomic data, and consensus methodology can determine if the current mechanistic repurposing categories have the highest chance of translational success or if other mechanistic avenues should be explored. With this increased focus on repurposed therapeutic strategies over de novo strategies, evolution and optimization of regulatory protections are needed to incentivize innovators and investigators.
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MR CLEAN，荷兰一项急性缺血性中风血管内治疗的多中心随机临床试验：随机对照试验的研究方案。
影响因子：
2.5
作者：
Fransen PS;Beumer D;Berkhemer OA;van den Berg LA;Lingsma H;van der Lugt A;van Zwam WH;van Oostenbrugge RJ;Roos YB;Majoie CB;Dippel DW;MR CLEAN Investigators
通讯作者：
MR CLEAN Investigators
影响因子：
9.9
作者：
Clark, WM;Warach, SJ;Sabounjian, LA
通讯作者：
Sabounjian, LA
影响因子：
46.9
作者：
Garber, Ken
通讯作者：
Garber, Ken
影响因子：
4.1
作者：
Fagan, Susan C.
通讯作者：
Fagan, Susan C.
影响因子：
4.7
作者：
Hernandez JJ;Pryszlak M;Smith L;Yanchus C;Kurji N;Shahani VM;Molinski SV
通讯作者：
Molinski SV