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标题: TKM-Ebola试验药成功治疗感染埃博拉病毒的猴子 [打印本页]

作者: ipsvirus 时间: 2015-4-23 16:06
标题: TKM-Ebola试验药成功治疗感染埃博拉病毒的猴子

日前，科研人员对一批猴子进行了埃博拉病毒药物实验，实验结果非常喜人。据悉，该种药物是在猴子感染埃博拉病毒72小时后注射进去的，它们让猴子保住了性命。这也预示着它将很有可能对人类也有效果。现在，这种药物正被送往塞拉利昂进行人体测试。上周，该地区只出现了9起埃博拉病毒感染病例。虽然埃博拉病毒现在西非的传播速度已经较之以前下降了许多，但对于生活在那里的人们来说，这场战斗远还没有结束。

据统计，自埃博拉病毒爆发之后，感染总人数达到了25,900，死亡人数10,700。这也就是科研人员要研发出预防病毒感染疫苗以及治疗药物显得那么重要的原因所在--它仍旧关系着人们的生与死。

实验中，科研人员首先向6只恒河猴体内注射足够致死剂量的埃博拉病毒。等到72个小时后，他们向其中3只猴子体内静脉注射一种被称为TKM-Ebola的药物。9天之后，注射了TKM-Ebola的猴子活了下来，另外一组则不幸死去。

获悉，TKM-Ebola一开始是为对抗扎伊尔基奎特（非西非地区）那里的埃博拉病毒而研发。德州大学埃博拉病毒研究者、该测试项目组成员Thomas Geisbert称，他们已经于去年在美国向大量的埃博拉病患注射了这种药物，并且所有人都活了下来，不过由于他们注射了多种药物，所以研究人员也没法确定就一定是TKM-Ebola起到的作用。

TKM通过阻止人体生成特定埃博拉蛋白质这种方法进行治疗。Geisbert介绍称，只要人体不产生病毒蛋白质，那么它就没法对人体构成威胁。另外，埃博拉病毒产生的其中一种蛋白质将会干扰人体的免疫系统，也就是说，TKM可以间接地帮助受感染猴子拥有对抗埃博拉病毒的能力。

虽然这种药物看起来非常具有前景，但由于它需要静脉注射，所以推行起来要比直接服用的药物困难很多。另外，它是否对人体也有治疗效果也还有待考证。

An experimental drug has cured monkeys infected with the Ebola virus, US-based scientists have said.

The treatment, known as TKM-Ebola-Guinea, targets the Makona strain of the virus, which caused the current deadly outbreak in West Africa.

All three monkeys receiving the treatment were healthy when the trial ended after 28 days; three untreated monkeys died within nine days.

Scientists cautioned that the drug's efficacy has not been proven in humans.

At present, there are no treatments or vaccines for Ebola that have been proven to work in humans.

University of Texas scientist Thomas Geisbert, who was the senior author of the study published in the journal Nature, said: "This is the first study to show post-exposure protection... against the new Makona outbreak strain of Ebola-Zaire virus."

Results from human trials with the drug are expected in the second half of this year.

Gene blocking

Mr Geisbert said the drug, produced by Tekmira Pharmaceuticals, could be adapted to target any strain of Ebola and could be manufactured in as little as eight weeks.

It works by blocking particular genes, which stops the virus replicating.

The two-month production time compares with the several months needed to make ZMapp - another experimental drug, which cured monkeys with a different strain of Ebola than the one in the current outbreak.

Since March 2014, more than 10,602 people have been reported as having died from the disease in six countries - Liberia, Guinea, Sierra Leone, Nigeria, the US and Mali.

The total number of reported cases is more than 25,556.

It has been the deadliest occurrence of Ebola since its discovery in 1976.

http://www.bbc.com/news/world-32424145

作者: marine0425030 时间: 2015-4-23 19:02
好消息啊。。楼主，辛苦了，多谢分享。有这个药物作用机制的文章吗？

作者: ipsvirus 时间: 2015-4-23 20:08

marine0425030 发表于 2015-4-23 19:02
好消息啊。。楼主，辛苦了，多谢分享。有这个药物作用机制的文章吗？

TKM-Ebola is an experimental drug for Ebola disease.

TKM-Ebola is being developed by Tekmira Pharmaceuticals Corp., a company located in Vancouver, Canada.The drug was formerly known as Ebola-SNALP.

It is a combination of Small interfering RNAs targeting three of the seven proteins in Ebola virus: Zaire Ebola L polymerase, Zaire Ebola membrane-associated protein (VP24), and Zaire Ebola polymerase complex protein (VP35), formulated with Tekmira's lipid nanoparticle technology.

（From the wikipedia）

作者: marine0425030 时间: 2015-4-23 20:17

哈哈，谢谢。。siRNA 啊。。不错，不错。。

作者: ipsvirus 时间: 2015-6-24 16:09
最近临床数据表明，这一备受期待的埃博拉药物因在临床试验中并未出现明显疗效而被终止（该药物此前在猴子实验中曾表现出较好结果）。

该药物研究方——加拿大本拿比埃尔迈拉制药公司和资助该药物研发的英国惠康基金会——近日宣布，它们将不再招募患者，因为这项实验已经到达了“预定义统计终点”。此前的研究结果表明，增加更多患者“并不能证明对患者的整体治疗益处”，惠康基金会在声明中说。

科学家仍然需要分析收集的数据以更深入地了解这种名为TKM-埃博拉-几内亚的药物如何会产生耐药性及其对疾病结果有何特定意义，英国牛津大学教授、研究负责人Peter Horby说。这项药物研发今年3月在塞拉利昂坡特洛科开始启动，旨在招募100名患者。但该公司并未公布现在已招募了多少名患者。

此次药物研究面临着若干障碍，美国得克萨斯大学加尔维斯顿医学分部科学家Thomas Geisbert说，他曾通过猴子检测TKM-埃博拉的有效性。TKN-埃博拉-几内亚是一套包裹在脂质纳米粒中的小核糖核酸分子，这种核糖核酸会干扰3种埃博拉蛋白并阻止病毒繁殖。Geisbert表示，用于人体临床试验的脂质纳米粒是一种比猴子实验都历时更久的配方。他表示，在此前的实验中，旧版本的脂质纳米粒仅能有效防止一半猴子繁殖病毒。“这是在把苹果和金桔作对比。”他说，但是新配方并未经过人体第一阶段安全试验，因此不能用于埃博拉患者。

试验设计也是一项挑战，Geisbert说。很多研究人员表示，给患者分配安慰剂组不合乎伦理规范，因此TKM-埃博拉试验只是一种所谓的随访研究，治疗中心的每位患者都会接收到药物，然后他们的生存几率会被用来与治疗中心那些未参与试验的患者进行对比，但是这样做会让数据结果很难解释，Geisbert说。

“这样做不能得出任何合理的结论。我怀疑这样做出的结果很难说明药物是否可以惠及患者。这次试验的结果不应该作为药物研究的终点。”他说，“如果没有找到答案，就要终止药物研究吗？这样做有些疯狂。

One of the highly anticipated trials of an Ebola drug that showed promising results in monkeys has been stopped early after it apparently failed to show a benefit to patients.

The company that developed the drug, Tekmira Pharmaceuticals of Burnaby, Canada, and the Wellcome Trust, which sponsored the trial, announced today that they would not enroll any more patients because the trial had reached “a predefined statistical endpoint.” Early results suggest that adding more patients to the study “was unlikely to demonstrate an overall therapeutic benefit to patients,” the Wellcome Trust said in its statement.

Scientists still have to analyze the data collected to learn more about how well the drug, called TKM-Ebola-Guinea, was tolerated and what specific effects it had on disease outcomes, says Peter Horby of the University of Oxford in the United Kingdom, who headed the study. The trial, which started in March in Port Loko, Sierra Leone, aimed to enroll 100 patients. The company did not say how many patients had been enrolled so far.

The drug faced several hurdles in the trial, says Thomas Geisbert of the University of Texas Medical Branch in Galveston, who tested TKM-Ebola in monkeys and found it protected all three of the animals that received it from an otherwise lethal dose of Ebola. TKM-Ebola-Guinea is a set of small RNA molecules packaged in lipid nanoparticles. The RNA interferes with three Ebola proteins and prevents the virus from replicating. Geisbert says the lipid nanoparticles used in the human trial are an older formulation than the one in the recent monkey trials. The older version protected only about half the monkeys in earlier tests, he says. “You’re comparing apples and kumquats,” he says. But the new formulation hadn’t been through phase I safety trials in humans and so couldn’t be used in Ebola patients.

The design of the trial was also a challenge, Geisbert says. Many say that assigning patients to a placebo arm is not ethical, so the TKM-Ebola trial was a so-called single-arm study in which everyone at a treatment center receives the drug and their survival is compared with patients at centers not involved in the trial. But that makes outcome data very hard to interpret, Geisbert says. “You can’t draw any reasonable conclusions. I doubt that anything comes out that is going to say one way or another” whether the drug benefits patients. The trial’s end shouldn’t be the end of the drug, he says. “If you can’t get an answer, and then you want to kill the drug? That’s crazy.”

The other drug seen as the best shot at fighting Ebola, the antibody cocktail ZMapp, is still being evaluated in a trial. The National Institute of Allergy and Infectious Diseases (NIAID) launched the trial in February in Liberia and the United States. It later expanded to Sierra Leone and is about to enroll patients in Guinea as well, says Anthony Fauci, who heads NIAID, located in Bethesda, Maryland.

The ZMapp trial is a different design from the TKM-Ebola trial. It randomly assigns patients to receive either three infusions of ZMapp plus supportive care or only supportive care, which includes intravenous fluids and treatment of secondary infections. Fauci is optimistic that the ZMapp trial will yield a clear answer. More than 30 patients have been enrolled already, he says. “We are likely to need many more patients than that to get a result, but less than 100.” With Guinea added to the trial, that goal should be reachable, he says.

http://news.sciencemag.org/afric ... company-halts-trial

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