Why is it so hard to cure ALS? - Fernando G. Vieira

翻译人员: Riley WANG 校对人员: Lipeng Chen

生活中没有什么是需要畏惧的， 只是需要了解。

现在我们去了解更多，就会畏惧更少。 ——玛丽·居里

In 1963, a 21-year-old physicist named Stephen Hawking

1963年，21岁的物理学家斯蒂芬·霍金

was diagnosed with a rare neuromuscular disorder

被诊断出一种罕见的神经肌肉失调症，

called amyotrophic lateral sclerosis, or ALS.

称为肌萎缩侧索硬化，也称为ALS。

Gradually, he lost the ability to walk,

霍金逐渐不能行走，

use his hands,

无法使用双手，

move his face,

不能做出面部动作，

and even swallow.

甚至不能吞咽。

But throughout it all, he retained his incredible intellect,

但尽管如此，他仍保留了惊人的才智。

and in the more than 50 years that followed,

在接下来的50多年中，

Hawking became one of history’s most accomplished and famous physicists.

霍金成为了历史上最著名、 最有成就的物理学家之一。

However, his condition went uncured

然而他的疾病依然未得到治愈，

and he passed away in 2018 at the age of 76.

霍金于2018年去世，享年76岁。

Decades after his diagnosis,

自霍金被诊断后的数十年来，

ALS still ranks as one of the most complex,

ALS仍然是最复杂、

mysterious,

最难以理解、

and devastating diseases to affect humankind.

对人类伤害最大的疾病之一。

Also called motor neuron disease and Lou Gehrig’s Disease,

这种疾病也被称为运动神经元病、卢伽雷病，

ALS affects about two out of every 100,000 people worldwide.

世界上每10万人中便有2人患有ALS。

When a person has ALS,

患上ALS时，

their motor neurons,

负责控制身体全部随意肌的细胞，

the cells responsible for all voluntary muscle control in the body,

即运动神经元，

lose function and die.

会失去功能，然后死亡。

No one knows exactly why or how these cells die

没有人知道这些细胞死亡的确切原因及方式，

and that’s part of what makes ALS so hard to treat.

这也是ALS难以治愈的原因之一。

In about 90% of cases,

在90%的病例中，

the disease arises suddenly, with no apparent cause.

ALS突然发作并且没有明显的病因。

The remaining 10% of cases are hereditary,

余下10%的病例则是通过遗传获得，

where a mother or father with ALS passes on a mutated gene to their child.

患者的父亲或母亲患有ALS 并将突变基因传给孩子。

The symptoms typically first appear after age 40.

ALS的症状通常在40岁时初次出现。

But in some rare cases, like Hawking’s, ALS starts earlier in life.

但个别病例，例如霍金，ALS的发病更早。

Hawking’s case was also a medical marvel because of how long he lived with ALS.

霍金在患有ALS的情况下生活了很长一段时间， 这也是一项医学奇迹。

After diagnosis, most people with the disease live between 2 to 5 years

大部分患者在诊断后只有2-5年的寿命，

before ALS leads to respiratory problems that usually cause death.

因最终ALS会使呼吸困难进而导致死亡。

What wasn’t unusual in Hawking’s case was that his ability to learn,

霍金身上不寻常的一点在于，

他的学习能力、思考能力

think,

and perceive with his senses remained intact.

以及通过感官认知的能力都毫发无伤。

Most people with ALS do not experience impaired cognition.

大多数患有ALS的患者不会出现认知受损。

With so much at stake for the 120,000 people

患上ALS要面临如此多的风险，

who are diagnosed with ALS annually,

而每年都有12万人次被诊断出患有该疾病，

curing the disease has become one of our most important scientific

治愈这种疾病已成为

最为重要的科学及医疗难题之一。

and medical challenges.

Despite the many unknowns,

尽管仍有大量未知，

we do have some insight into how ALS impacts the neuromuscular system.

我们对ALS如何影响神经肌肉系统已有所了解。

ALS affects two types of nerve cells called the upper and lower motor neurons.

ALS会影响两种类型的神经细胞，

上运动神经元和下运动神经元。

In a healthy body, the upper motor neurons,

在健康的身体中，

位于大脑皮层的上神经元细胞将大脑发出的信号 传递给下运动神经元，

which sit in the brain’s cortex,

transmit messages from the brain to the lower motor neurons,

situated in the spinal cord.

下运动神经元位于脊髓中。

Those neurons then transmit the message into muscle fibers,

这些神经元再将信息传递给肌肉纤维，

which contract or relax in response,

使其做出收缩或放松的反应，

resulting in motion.

完成动作。

Every voluntary move we make occurs

我们做出的每个自发性动作，

because of messages transmitted along this pathway.

都是由于信息沿神经通路传导。

But when motor neurons degenerate in ALS,

但患上ALS时运动神经元退化，

their ability to transfer messages is disrupted,

其传输信息的能力中断，

and that vital signaling system is thrown into chaos.

重要的信号系统陷入混乱。

Without their regular cues, the muscles waste away.

没有了规律的信号指令，肌肉很快萎缩。

Precisely what makes the motor neurons degenerate

ALS最大的谜团在于

is the prevailing mystery of ALS.

运动神经元退化的确切原因。

In hereditary cases, parents pass genetic mutations on to their children.

在遗传患病的病例中， 父母将基因突变传递给孩子。

Even then, ALS involves multiple genes

此时仍有多个基因与ALS相关，

with multiple possible impacts on motor neurons,

对运动神经元造成的可能影响也有多个，

making the precise triggers hard to pinpoint.

因此，精准锁定疾病的诱发因素十分困难。

When ALS arises sporadically, the list of possible causes grows:

当ALS症状偶有发生， 可能致病的因素会越来越多，

toxins,

毒素、

viruses,

病毒、

lifestyle,

生活方式、

or other environmental factors may all play roles.

其他环境因素等， 它们都可能会产生一定影响。

And because there are so many elements involved,

由于涉及到如此多的因素，

there’s currently no single test that can determine whether someone has ALS.

目前没有单一的测试 能够确定患者是否患上了ALS。

Nevertheless, our hypotheses on the causes are developing.

尽管如此，我们对于患病原因的推想仍在发展。

One prevailing idea is that certain proteins inside the motor neurons

一个主流观点认为在运动神经元中，

aren’t folding correctly,

某种特定蛋白没有正确折叠，

and are instead forming clumps.

反而聚集成块。

The misfolded proteins and clumps may spread from cell to cell.

错误折叠的蛋白质和块状结构 可能会扩散到其他细胞，

This could be clogging up normal cellular processes,

这可能会堵塞正常的细胞进程，

like energy and protein production, which keep cells alive.

例如能量和蛋白质的产生过程， 这一过程能保持细胞充满活力。

We’ve also learned that along with motor neurons and muscle fibers,

我们也已经知道， 除了运动神经元和肌肉纤维，

ALS could involve other cell types.

ALS也涉及到其他细胞类型。

ALS patients typically have inflammation in their brains and spinal cords.

ALS患者的大脑和脊髓通常都有炎症。

Defective immune cells may also play a role in killing motor neurons.

有缺陷的免疫细胞可能 也会消灭运动神经元细胞。

And ALS seems to change the behavior of specific cells

ALS似乎能够改变某种特定细胞的行为，

that provide support for neurons.

这种细胞为神经元提供支持。

These factors highlight the disease’s complexity,

这些因素表明了ALS疾病的复杂性，

but they may also give us a fuller understanding of how it works,

但是它们也让我们更全面地了解发病机制，

opening up new avenues for treatment.

为治疗打开了新的大门。

And while that may be gradual, we’re making progress all the time.

虽然进程也许缓慢，但我们一直在取得进步。

We’re currently developing new drugs,

我们现在正在开发新药，

new stem cell therapies to repair damaged cells,

新的干细胞疗法用来修复受损细胞，

and new gene therapies to slow the advancement of the disease.

以及新的基因疗法用以减缓疾病发展速度。

With our growing arsenal of knowledge,

在不断积累知识储备的同时，

we look forward to discoveries that can change the future

我们期待能够有新的发现，

来改变ALS患者的未来。

for people living with ALS.