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Creutzfeldt-Jakob disease
克雅氏病
Breaking down the barrier
攻破屏障
A glimmer of hope for a drug that treats diseasecaused by prions
药物治疗朊病毒感染疾病的一线希望
THE epidemic of mad-cow disease in people that some forecast in the 1990s has not,fortunately, come to pass. But Creutzfeldt-Jakob disease, to give its proper name, is still anasty illness that humanity would be better off without.
时至今日，疯牛病没有像上世纪90年代的某些预言说的那样在人群中流行，真是幸运。这种严重损害人类性情的疾病的准确名称叫克雅氏病，治疗起来仍然棘手。
It is also a strange illness.
克雅氏病是一种奇怪的疾病。
CJD and a handful of similarneurological conditions are caused by the misfolding of a particular protein that is found inthe membranes of certain nerve cells.
该病以及类似的一些神经症状是由于某种神经细胞的细胞膜上的一个特殊蛋白发生错误折叠所致。
The strangeness is that the misfolded protein, known as a prion, somehow catalyses othermolecules of the protein to misfold in the same way.
这种错误折叠的蛋白称为朊病毒，令人奇怪的是它可以催化其他蛋白分子发生相同的错误折叠，
The result is a chain reaction in which more and more protein ends up as prions.
这个链式反应使越来越多的蛋白质变成朊病毒。
Nerve cells containing the prions stop working.
含有朊病毒的神经细胞失去正常功能，
The sufferer endures memory loss, personality changes and spontaneous, jerky bodilymovements.
罹患者出现记忆减退、人格改变和自发的躯体急速抽动等症状，
Eventually, the disease kills him.
最后患者死亡。
A drug to treat CJD would therefore be welcome.
所以，能够治疗CJD的药物将大受青睐。
And chemicals that seem either to prevent the misfolding, or to help the body clear awaymisfolded molecules, do, indeed, exist.
能阻止分子错误折叠或帮助机体清除错误折叠分子的化学药品似乎确实存在，
The problem is turning at least one of those chemicals into an effective medicine.
困难在于如何用至少一种这样的化学药品进行有效治疗。
Adam Renslo of the University of California, San Francisco, and his colleagues have beentrying to do so.
旧金山加利福尼亚大学的Adam Renslo与其同事一直在进行将化学药品用于治疗CJD的尝试，
The chemicals they have lighted on are called aminothiazoles.
他们感兴趣的化学药品叫做氨噻唑，
These are quite effective in reducing the prion levels of cultured nerve cells.
它能有效降低体外培养的神经细胞内的朊病毒水平。
Testing aminothiazoles in Petri dishes is, however, rather different from testing them on livinganimals.
但是，检验发现氨噻唑在活动物体内的作用与在体外培养细胞中的作用大不相同。
A natural barrier exists between the bloodstream and the brain, to protect it from harmfulchemicals.
生理状态下，血流与脑之间存在着一个屏障，使脑避免接触有害物质，
This barrier interprets many putative drugs, including aminothiazoles, as harmful, and thuskeeps them out.
可能有效的许多药物包括氨噻唑也被这个屏障当作有害物质阻挡在脑外。
And if a molecule cannot cross the barrier, it will not make an effective neurologicaltreatment.
不能通过屏障进入脑的分子当然就无法完成有效的神经治疗。
Dr Renslo and his colleagues have therefore been analysing and modifying the chemicalstructure of aminothiazoles to see if this can enable them to cross the blood-brain barrier.
为此，Renslo博士与其同事已经在分析并尝试修饰氨噻唑的分子结构，以使之能通过血脑屏障。
As they report in the Journal of Medicinal Chemistry, they think they have now pulled off thetrick.
根据他们在药物化学杂志的报道，他们已经找到了突破口。
They did it by removing groups of atoms called hydrogen-bond donors from the originalmolecules and adding a ring of carbon and hydrogen atoms.
他们移除氨噻唑分子上一组提供氢键的原子，并加上一个碳氢环。修饰后的氨噻唑分子看起来更像胆固醇分子。
That made the aminothiazoles look more like cholesterolwhich despite its malign everydayreputation is an important component of brains and routinely crosses the blood-brainbarrier.
尽管胆固醇整天被认为是个对人体有害的物质，但它却是脑的重要成分，是通过血脑屏障的常客。
It worked.
成功了!
When Dr Renslo fed mice a diet containing the improved aminothiazoles, he found that themost promising of them accumulated in the brain in concentrations nearly 25 times higherthan those required to clear prions from cultured cells.
Renslo博士给小鼠喂食含有改进后的氨噻唑的饮食后，发现这些最有希望的分子在小鼠的脑内聚集，其浓度达到清除体外培养细胞内朊病毒所需浓度的25倍。
The molecular changes did not, though, seem to change the aminothiazoles prion-killingattributes.
氨噻唑分子的改变似乎并没有改变其杀灭朊病毒的特性。
When tested in Petri dishes, the new molecules were as good as their precursors.
在培养皿实验中，修饰后的分子与其前体一样有效。
More importantly, preliminary results suggest they are effective at extending the lives ofprion-infected mice.
更重要的是，初步的实验结果提示这些分子能有效延长朊病毒感染小鼠的寿命，
Such mice lived for 100 days longer when treated with the new molecules than they didwhen untreated.
用这些新分子治疗的小鼠比不治疗的小鼠多存活100天。
That is a significant fraction of the two to three years a healthy laboratory mouse might beexpected to survive if it is not experimented on.
考虑到实验室中未受试的健康小鼠的预期寿命是2到3年，染毒小鼠获得延长的这部分存活期显得很显著了。
Trials in mice are, of course, just the beginning. But breaching the blood-brain barrier in thisway is a crucial step, and one that might be generalised to potential treatments for otherbrain diseasesAlzheimer s, for example.
当然，用小鼠进行的试验只是个开始。但药物以这种方式突破血脑屏障确实是个关键步骤，在此基础上，人们还可能找到治疗阿尔茨海默尔病这样的其他脑部疾病的良方。
If that came to pass, this small step on the journey of drug discovery might come to be seen,in retrospect, as a giant leap.
在达到那些目标之后，回过头来看，实现药物通过屏障的这一小步将被视为一个巨大的跨步。
词语解释
1.disease n.疾病
The disease is still in its primary stage.
这疾病仍然在初发阶段。
2.forecast n.预测;预报
Share prices plunged as a result of the gloomyeconomic forecast.
关于经济前景暗淡的预测导致股票价格大跌。
3.humanity n.人类;人性
Such a man is a stain to humanity.
这种人是人类的耻辱。
4.membrane n.薄膜;膜状物
A plastic membrane serves as selective diffusion barrier.
一层塑料薄膜起着选择性渗透屏障的作用。
5.protein n.蛋白质
You need more protein to build you up.
你需要增加蛋白质以增强体质。
Creutzfeldt-Jakob disease
克雅氏病
Breaking down the barrier
攻破屏障
A glimmer of hope for a drug that treats diseasecaused by prions
药物治疗朊病毒感染疾病的一线希望
THE epidemic of mad-cow disease in people that some forecast in the 1990s has not,fortunately, come to pass. But Creutzfeldt-Jakob disease, to give its proper name, is still anasty illness that humanity would be better off without.
时至今日，疯牛病没有像上世纪90年代的某些预言说的那样在人群中流行，真是幸运。这种严重损害人类性情的疾病的准确名称叫克雅氏病，治疗起来仍然棘手。
It is also a strange illness.
克雅氏病是一种奇怪的疾病。
CJD and a handful of similarneurological conditions are caused by the misfolding of a particular protein that is found inthe membranes of certain nerve cells.
该病以及类似的一些神经症状是由于某种神经细胞的细胞膜上的一个特殊蛋白发生错误折叠所致。
The strangeness is that the misfolded protein, known as a prion, somehow catalyses othermolecules of the protein to misfold in the same way.
这种错误折叠的蛋白称为朊病毒，令人奇怪的是它可以催化其他蛋白分子发生相同的错误折叠，
The result is a chain reaction in which more and more protein ends up as prions.
这个链式反应使越来越多的蛋白质变成朊病毒。
Nerve cells containing the prions stop working.
含有朊病毒的神经细胞失去正常功能，
The sufferer endures memory loss, personality changes and spontaneous, jerky bodilymovements.
罹患者出现记忆减退、人格改变和自发的躯体急速抽动等症状，
Eventually, the disease kills him.
最后患者死亡。
A drug to treat CJD would therefore be welcome.
所以，能够治疗CJD的药物将大受青睐。
And chemicals that seem either to prevent the misfolding, or to help the body clear awaymisfolded molecules, do, indeed, exist.
能阻止分子错误折叠或帮助机体清除错误折叠分子的化学药品似乎确实存在，
The problem is turning at least one of those chemicals into an effective medicine.
困难在于如何用至少一种这样的化学药品进行有效治疗。
Adam Renslo of the University of California, San Francisco, and his colleagues have beentrying to do so.
旧金山加利福尼亚大学的Adam Renslo与其同事一直在进行将化学药品用于治疗CJD的尝试，
The chemicals they have lighted on are called aminothiazoles.
他们感兴趣的化学药品叫做氨噻唑，
These are quite effective in reducing the prion levels of cultured nerve cells.
它能有效降低体外培养的神经细胞内的朊病毒水平。
Testing aminothiazoles in Petri dishes is, however, rather different from testing them on livinganimals.
但是，检验发现氨噻唑在活动物体内的作用与在体外培养细胞中的作用大不相同。
A natural barrier exists between the bloodstream and the brain, to protect it from harmfulchemicals.
生理状态下，血流与脑之间存在着一个屏障，使脑避免接触有害物质，
This barrier interprets many putative drugs, including aminothiazoles, as harmful, and thuskeeps them out.
可能有效的许多药物包括氨噻唑也被这个屏障当作有害物质阻挡在脑外。
And if a molecule cannot cross the barrier, it will not make an effective neurologicaltreatment.
不能通过屏障进入脑的分子当然就无法完成有效的神经治疗。
Dr Renslo and his colleagues have therefore been analysing and modifying the chemicalstructure of aminothiazoles to see if this can enable them to cross the blood-brain barrier.
为此，Renslo博士与其同事已经在分析并尝试修饰氨噻唑的分子结构，以使之能通过血脑屏障。
As they report in the Journal of Medicinal Chemistry, they think they have now pulled off thetrick.
根据他们在药物化学杂志的报道，他们已经找到了突破口。
They did it by removing groups of atoms called hydrogen-bond donors from the originalmolecules and adding a ring of carbon and hydrogen atoms.
他们移除氨噻唑分子上一组提供氢键的原子，并加上一个碳氢环。修饰后的氨噻唑分子看起来更像胆固醇分子。
That made the aminothiazoles look more like cholesterolwhich despite its malign everydayreputation is an important component of brains and routinely crosses the blood-brainbarrier.
尽管胆固醇整天被认为是个对人体有害的物质，但它却是脑的重要成分，是通过血脑屏障的常客。
It worked.
成功了!
When Dr Renslo fed mice a diet containing the improved aminothiazoles, he found that themost promising of them accumulated in the brain in concentrations nearly 25 times higherthan those required to clear prions from cultured cells.
Renslo博士给小鼠喂食含有改进后的氨噻唑的饮食后，发现这些最有希望的分子在小鼠的脑内聚集，其浓度达到清除体外培养细胞内朊病毒所需浓度的25倍。
The molecular changes did not, though, seem to change the aminothiazoles prion-killingattributes.
氨噻唑分子的改变似乎并没有改变其杀灭朊病毒的特性。
When tested in Petri dishes, the new molecules were as good as their precursors.
在培养皿实验中，修饰后的分子与其前体一样有效。
More importantly, preliminary results suggest they are effective at extending the lives ofprion-infected mice.
更重要的是，初步的实验结果提示这些分子能有效延长朊病毒感染小鼠的寿命，
Such mice lived for 100 days longer when treated with the new molecules than they didwhen untreated.
用这些新分子治疗的小鼠比不治疗的小鼠多存活100天。
That is a significant fraction of the two to three years a healthy laboratory mouse might beexpected to survive if it is not experimented on.
考虑到实验室中未受试的健康小鼠的预期寿命是2到3年，染毒小鼠获得延长的这部分存活期显得很显著了。
Trials in mice are, of course, just the beginning. But breaching the blood-brain barrier in thisway is a crucial step, and one that might be generalised to potential treatments for otherbrain diseasesAlzheimer s, for example.
当然，用小鼠进行的试验只是个开始。但药物以这种方式突破血脑屏障确实是个关键步骤，在此基础上，人们还可能找到治疗阿尔茨海默尔病这样的其他脑部疾病的良方。
If that came to pass, this small step on the journey of drug discovery might come to be seen,in retrospect, as a giant leap.
在达到那些目标之后，回过头来看，实现药物通过屏障的这一小步将被视为一个巨大的跨步。
词语解释
1.disease n.疾病
The disease is still in its primary stage.
这疾病仍然在初发阶段。
2.forecast n.预测;预报
Share prices plunged as a result of the gloomyeconomic forecast.
关于经济前景暗淡的预测导致股票价格大跌。
3.humanity n.人类;人性
Such a man is a stain to humanity.
这种人是人类的耻辱。
4.membrane n.薄膜;膜状物
A plastic membrane serves as selective diffusion barrier.
一层塑料薄膜起着选择性渗透屏障的作用。
5.protein n.蛋白质
You need more protein to build you up.
你需要增加蛋白质以增强体质。
