美国国家公共电台 NPR After A Big Failure, Scientists And Patients Hunt For A New Type Of Alzheimer's Drug

After A Big Failure, Scientists And Patients Hunt For A New Type Of Alzheimer's Drug

AUDIE CORNISH, HOST:

Scientists are changing course in their quest to treat Alzheimer's disease. The new direction comes after a series of failures with drugs aimed at a toxic¹ protein called amyloid-beta. Now researchers are pinning their hopes on drugs that have other targets, and as NPR's Jon Hamilton reports, so are patients.

JON HAMILTON, BYLINE²: Phil Gutis was 54 when he was diagnosed with Alzheimer's; that was three years ago.

PHIL GUTIS: I'm just being erased³ - all these memories, you know, the memory of my dog.

HAMILTON: His dog Abe, a Jack⁴ Russell who died last year. A few weeks ago, Gutis found himself leafing through pictures of Abe and trying to remember the dog who'd shared his life for 12 years.

GUTIS: But there were no memories. There were no memories of me and him. And then I told a friend about this, and she said, you don't remember walking on the trail and how he used to scamper⁵ ahead and try to trip you and da-da-da (ph)? And I'm like, no, I don't.

HAMILTON: Until recently, Gutis thought he might be able to preserve at least some of his remaining memories. He'd been part of a trial of an experimental drug called aducanumab.

GUTIS: Participating in this trial, it gave me hope for the future.

HAMILTON: There'd been a lot of excitement about the drug because it was really good at removing amyloid-beta from the brain. But in March, researchers announced that it didn't prevent dementia. Gutis says the news was a huge disappointment for both patients and researchers.

GUTIS: I think the scientists have largely said, OK, we give up, because this is - I mean, many drugs targeting this have now failed.

HAMILTON: So scientists are trying to figure out what comes next. They're looking at a range of strategies, from modulating⁶ the brain's immune system to protecting healthy brain cells. Dr. Daniel Alkon is president and chief scientific officer of a company called Neurotrope. He says the scientific community learned something important from all those failures with amyloid drugs.

DANIEL ALKON: Dealing⁷ with the amyloid is probably important, but it's not going to be sufficient.

HAMILTON: Alkon had suspected that for years. He'd spent decades as a researcher who studied memory and the wiring that allows brain cells to communicate. And that led him to focus on a feature of Alzheimer's that didn't involve amyloid.

ALKON: One of the earliest events in Alzheimer's disease is the loss of that wiring. And as the wiring loss progresses, the cognitive⁸ function loss progresses.

HAMILTON: So Alkon and a team of researchers studied mice that had been genetically⁹ altered to develop a condition similar to Alzheimer's. And he says they realized something surprising.

ALKON: You saw this very significant loss of wiring, and you could actually reverse it; you could regenerate¹⁰ the wiring.

HAMILTON: By creating new connections between brain cells. This process was controlled by a protein called PKC-epsilon. Alkon says the team thought, if they could find a way to tweak PKC-epsilon, maybe they could get the brain to replace some of the wiring lost in Alzheimer's.

ALKON: We asked, is there any drug, known drug, in the world that can target PKC-epsilon safely, without hurting a patient?

HAMILTON: And they found one - It's called bryostatin-1, and it comes from a marine¹¹ animal often mistaken for seaweed. Decades ago, researchers at the National Cancer Institute studied bryostatin-1 as a treatment for cancer; that effort didn't work out. But Alkon thought the drug might work for Alzheimer's because it had a dramatic effect on PKC-epsilon. So his team tried it, first on animals and then a small group of people, including a man named Frank.

ALKON: He had been sitting in a chair, staring at the ceiling, hallucinating. Within a couple of weeks of our treating him, he started swimming, playing pool, communicating, feeding himself.

HAMILTON: Two preliminary studies hinted that patients with advanced Alzheimer's could get better with bryostatin-1, and a more rigorous study of about 150 people suggested a modest benefit. So now Neurotrope is working to confirm those results. And of course, bryostatin-1 is just one potential Treatment. Several others target a toxic substance called tau that builds up inside the brain cells of Alzheimer's patients. And Dr. Steven Arnold of Harvard Medical School says, still, other drugs target inflammation or the way that brain cells clear out toxins¹².

STEVEN ARNOLD: These are all really powerful ways in which we can perhaps prevent, delay or even reverse Alzheimer's disease.

HAMILTON: Arnold says there's growing interest in drugs that can protect brain cells and help them function better.

ARNOLD: If we do that, we may find that it's not only good for Alzheimer's disease, but it's also good for other degenerative conditions of the brain, like Parkinson's disease.

HAMILTON: In the meantime, Alzheimer's patients like Phil Gutis continue to look for anything that might help. Gutis says he was devastated¹³ when the drug trial he'd been in was halted, but he says he'd welcome the chance to try again.

GUTIS: I mean, it's probably going to be at least a year before I'm eligible¹⁴ to be in another medical trial. But I would - in a second.

HAMILTON: Jon Hamilton, NPR News.

1 toxic   

adj.有毒的，因中毒引起的

参考例句：

• The factory had accidentally released a quantity of toxic waste into the sea.这家工厂意外泄漏大量有毒废物到海中。
• There is a risk that toxic chemicals might be blasted into the atmosphere.爆炸后有毒化学物质可能会进入大气层。

2 byline   

n.署名；v.署名

参考例句：

• His byline was absent as well.他的署名也不见了。
• We wish to thank the author of this article which carries no byline.我们要感谢这篇文章的那位没有署名的作者。

3 erased   

v.擦掉( erase的过去式和过去分词 )；抹去；清除

参考例句：

• He erased the wrong answer and wrote in the right one. 他擦去了错误答案，写上了正确答案。 来自《简明英汉词典》
• He removed the dogmatism from politics; he erased the party line. 他根除了政治中的教条主义，消除了政党界限。 来自《简明英汉词典》

4 jack   

n.插座，千斤顶，男人；v.抬起，提醒，扛举；n.（Jake）杰克

参考例句：

• I am looking for the headphone jack.我正在找寻头戴式耳机插孔。
• He lifted the car with a jack to change the flat tyre.他用千斤顶把车顶起来换下瘪轮胎。

5 scamper   

v.奔跑，快跑

参考例句：

• She loves to scamper through the woods of the forest.她喜欢在森林里的树林中穿梭嬉戏。
• The flash sent the foxes scampering away.闪光惊得狐狸四处逃窜。

6 modulating   

调整( modulate的现在分词 )； （对波幅、频率的）调制； 转调； 调整或改变（嗓音）的音调

参考例句：

• In his horn solo,he kept modulating from key to key. 他在喇叭独奏时不断地变调。
• Water vapour and clouds are the primary variables modulating direct solar absorption. 水汽和云是调节直接太阳吸收的主要要素。

7 dealing   

n.经商方法，待人态度

参考例句：

• This store has an excellent reputation for fair dealing.该商店因买卖公道而享有极高的声誉。
• His fair dealing earned our confidence.他的诚实的行为获得我们的信任。

8 cognitive   

adj.认知的，认识的，有感知的

参考例句：

• As children grow older,their cognitive processes become sharper.孩子们越长越大，他们的认知过程变得更为敏锐。
• The cognitive psychologist is like the tinker who wants to know how a clock works.认知心理学者倒很像一个需要通晓钟表如何运转的钟表修理匠。

9 genetically   

adv.遗传上

参考例句：

• All the bees in the colony are genetically related. 同一群体的蜜蜂都有亲缘关系。
• Genetically modified foods have already arrived on American dinner tables. 经基因改造加工过的食物已端上了美国人的餐桌。 来自英汉非文学 - 生命科学 - 基因与食物

10 regenerate   

vt.使恢复，使新生；vi.恢复，再生；adj.恢复的

参考例句：

• Their aim is to regenerate British industry.他们的目的是复兴英国的工业。
• Although it is not easy,you have the power to regenerate your life.尽管这不容易，但你有使生活重获新生的能力。

11 marine   

adj.海的；海生的；航海的；海事的；n.水兵

参考例句：

• Marine creatures are those which live in the sea. 海洋生物是生存在海里的生物。
• When the war broke out,he volunteered for the Marine Corps.战争爆发时，他自愿参加了海军陆战队。

12 toxins   

n.毒素( toxin的名词复数 )

参考例句：

• The seas have been used as a receptacle for a range of industrial toxins. 海洋成了各种有毒工业废料的大容器。
• Most toxins are naturally excreted from the body. 大部分毒素被自然排出体外。 来自《简明英汉词典》

13 devastated   

v.彻底破坏( devastate的过去式和过去分词)；摧毁；毁灭；在感情上（精神上、财务上等）压垮adj.毁坏的；极为震惊的

参考例句：

• The bomb devastated much of the old part of the city. 这颗炸弹炸毁了旧城的一大片地方。
• His family is absolutely devastated. 他的一家感到极为震惊。

14 eligible   

adj.有条件被选中的；(尤指婚姻等)合适(意)的

参考例句：

• He is an eligible young man.他是一个合格的年轻人。
• Helen married an eligible bachelor.海伦嫁给了一个中意的单身汉。