In 2016, when Susannah Rosen was 2½ years old, her parents, Luke Rosen and Sally Jackson, noticed during bath time that something wasn't right. When Sally prompted Susannah to playfully kick her legs in the water, she wasn't able to.

2016年，当苏珊娜·罗森两岁半时，她的父母卢克·罗森和莎莉·杰克逊在洗澡时注意到有些不对劲。当莎莉促使苏珊娜在水中嬉戏地踢腿时，她却无法做到。

'For our first kid, if it was a bee sting, we would run into the emergency room, right? But we were like, she's our second kid, you know? She's gonna catch up on her own ... but she didn't catch up,' Luke said. 'After we found out she couldn't kick, we went to the hospital.'

‘我们的第一个孩子，如果是被蜜蜂蜇了，我们会马上跑进急诊室，对吧？但这是我们的第二个孩子，你知道的？她会自己赶上的……但她没有赶上，’卢克说。‘在我们发现她不能踢腿后，我们就去了医院。’

Luke and Sally were living with their two kids in New York City.  Luke had a thriving career as an actor and writer, and Sally was working as a chef's assistant.

卢克和莎莉与他们的两个孩子住在纽约市。卢克作为演员和作家有着蒸蒸日上的事业，而莎莉则在做厨师助理。

Luke said Susannah didn't have great balance as a toddler and needed assistance walking, common characteristics of a child learning a new milestone. But as time went on, the gap between Susannah's development and that of her peers started to widen.

卢克说，苏珊娜在幼儿时期平衡能力不太好，需要人扶着走路，这是一个孩子学习新技能时的常见特征。但随着时间推移，苏珊娜的发育与同龄人之间的差距开始拉大。

Sally Jackson, Luke Rosen and their daughter, Susannah Rosen

萨莉·杰克逊，卢克·罗森和他们的女儿，苏珊娜·罗森

'She was couch surfing and army crawling around the apartment at an age when toddlers typically take off running,' Luke recalled. When she tried to walk, Susannah had a wide gait and appeared unsteady and uncoordinated, often a symptom of an underlying problem.

“她那时本应像其他学步儿童一样到处跑跳，却只能在沙发上蹭来蹭去，像军人一样爬行，”卢克回忆道。当苏珊娜尝试走路时，她的步态很宽，看起来不稳且不协调，这通常是潜在问题的症状。

Susannah was diagnosed with a mutation in her KIF1A gene. The KIF1A gene gets its name from an important molecular motor protein that it creates that is vital to brain function. Mutations in this gene cause KIF1A-Associated Neurological Disorder, or KAND. When Susannah was diagnosed, Luke and Sally were told the mutation in her KIF1A gene was causing a 'toxic gain of function.'.

Susannah 被诊断出 KIF1A 基因发生了突变。KIF1A 基因的名字来源于它所创造的一种对大脑功能至关重要的分子马达蛋白。该基因的突变会导致 KIF1A 相关神经系统疾病（KAND）。当 Susannah 被诊断时，Luke 和 Sally 被告知她 KIF1A 基因的突变引起了“毒性功能获得”。

'When I heard that, I thought, oh, 'gain of function.' That's good!' Luke said. '[But] it's not good. The function that that gene gains gives off this really toxic element of protein that slowly kills the nerves in her brain and kills the nerves in her whole body.'

“当我听到这个消息时，我想，哦，‘功能获得’。那很好！”卢克说。“[但]这并不好。那个基因获得的功能释放出一种非常有毒的蛋白质元素，这种元素会慢慢杀死她大脑中的神经，并且杀死她全身的神经。”

More than 90% of patients diagnosed with KAND have developmental delays and intellectual disabilities, more than 80% have vision loss or impairment, and more than 40% have seizures. In addition, many experience other symptoms, ranging from diarrhea and constipation to kidney problems. Experts say no two patients are affected in the same way, which makes the disorder very difficult to properly diagnose.

超过 90% 的 KAND 患者存在发育迟缓和智力障碍，超过 80% 存在视力丧失或受损，超过 40% 存在癫痫发作。此外，许多患者还会经历其他症状，从腹泻、便秘到肾脏问题不等。专家表示，没有任何两名患者的受影响方式是相同的，这使得该疾病很难得到正确诊断。

According to .

根据。

KIF1A.org

KIF1A.org

, approximately 1 in 4 of those diagnosed with KIF1A mutations were originally misdiagnosed with cerebral palsy.

大约有四分之一的KIF1A基因突变患者最初被误诊为脑瘫。

Sally, Luke and Susannah on a stroll.

萨莉、卢克和苏珊娜在散步。

Courtesy: The Rosen Family

Courtesy: 罗森家族

At the time of Susannah's diagnosis, in 2016, there were no treatments for KIF1A, and no clinical trials underway or literature to lean on for answers. The Rosens were told that Susannah probably would not be able to walk and would likely suffer from seizures.

2016年苏珊娜确诊时，尚无针对KIF1A的治疗方法，也没有正在进行的临床试验或可参考的文献。罗森一家被告知，苏珊娜可能无法行走，并且可能会遭受癫痫发作。

'So there were a lot of tears in that room,' said Luke. 'That was the beginning of our incredibly new and terrifying normal.'

“所以那个房间里有很多眼泪，”卢克说。“那是我们全新且可怕的生活的开始。”

Susannah's physician, Dr. Wendy Chung, who is a CNBC Advisory Board member, told the Rosens that they had five years to find a treatment for Susannah before it would likely be too late. She recommended Luke and Sally try to find 100 patients with the same diagnosis as Susannah so that they could begin to better understand the disease and how it progresses.

苏珊娜的医生，同时也是CNBC顾问委员会成员的温迪·钟告诉罗森夫妇，他们有五年的时间来为苏珊娜找到治疗方法，否则很可能为时已晚。她建议卢克和莎莉尝试找到100名与苏珊娜相同诊断的患者，以便他们能够开始更好地了解这种疾病及其进展。

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CNBC Cures Susannah Rosen and Dr. Wendy Chung

CNBC治愈了苏珊娜·罗森和吴 Wendy 博士

Courtesy: The Rosen Family

Courtesy: 罗森家族

Luke and Sally started the

路克和莎莉开始了

KIF1A.org

KIF1A.org

Foundation shortly after Susannah's diagnosis. They hoped that by connecting with other families living with KAND, they could build a patient population large enough to start research that could eventually lead to a treatment discovery. Today, the foundation has been able to connect 700 families hoping to race against the clock together. .

在苏珊娜确诊后不久，基金会成立了。他们希望通过与其他生活在KAND中的家庭建立联系，能够建立起足够大的患者群体，以启动研究，最终可能导致治疗的发现。如今，该基金会已经能够联系到700个家庭，希望能够共同与时间赛跑。

'One of the things we realized about KIF1A is that it's not nearly as rare as we might think it is,' Chung said in a taped interview with KIF1A.org. 'We can see just over the past three years that we've been watching the numbers grow.'

“我们对 KIF1A 了解到的一件事是，它并不像我们想象的那么罕见，”钟在与 KIF1A.org 的录像采访中说道。“我们可以看到，仅仅在过去的三年里，我们观察到这个数字一直在增长。”

Those efforts eventually led them to the n-Lorem Foundation. Launched in 2020 by Ionis Pharmaceuticals founder and CNBC Advisory Board member Dr. Stanley Crooke, n-Lorem is a nonprofit organization that develops antisense oligonucleotide, or ASO, therapies for patients with nano-rare diseases and provides the treatments to the patients for free for life. Nano-rare is a term coined by Crooke to describe diseases that are extremely rare — affecting between one and 30 people worldwide.

这些努力最终将他们引向了n-Lorem基金会。该基金会于2020年由Ionis制药公司创始人、CNBC顾问委员会成员斯坦利·克鲁克博士创立，是一个非营利组织，致力于为患有“纳米罕见病”的患者开发反义寡核苷酸（ASO）疗法，并终身免费为患者提供治疗。“纳米罕见病”是克鲁克创造的一个术语，用来描述极其罕见的疾病——全球影响人数在1至30人之间。

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Susannah Rosen at the hospital for her ASO treatment.

苏珊娜·罗森在医院接受ASO治疗。

Courtesy: The Rosen Family

礼貌：罗森家族

'The FDA defines rare disease as a patient population of 200,000,' Crooke said in an interview with CNBC. 'But we now know that there are many, many pathogenic mutations that produce disease in far fewer patients ... And our focus is on these patients, because they have no hope.  You can imagine the isolation and the desperation and the lack of information that's available when you're one of 30.'.

“FDA将罕见病定义为患者群体为20万人，”克鲁克在接受CNBC采访时说，“但现在我们知道，有许多致病突变在远少于这个数的患者中引发疾病……我们的关注点是这些患者，因为他们没有希望。你可以想象，当你只是30人之一的时候，那种孤立、绝望以及信息的缺乏。”

Crooke estimates he has personally spent $10 million since 2020 on developing new drugs and treating the patients, a fraction of the amount the foundation has spent, he said. Patients with the same mutation can be treated with the same medicine, but if n-Lorem needs to develop a new treatment, the average cost is $1.2 million, he said..

克鲁克估计，自2020年以来，他个人已经在开发新药和治疗患者上花费了1000万美元，他说，这只是基金会花费金额的一小部分。他说，具有相同基因突变的患者可以使用相同的药物进行治疗，但如果n-Lorem需要开发一种新的治疗方法，平均成本为120万美元。

Since the foundation's launch, it's had more than 400 rare disease patient applicants, of which it has been able to accept about 200, Crooke said. Once accepted, the patient is added to a waitlist, and n-Lorem will soon begin treatment on the organization's 40th patient, he said.

克鲁克说，自从基金会成立以来，已经有400多名罕见病患者申请，其中大约200名被接受。一旦被接受，患者将被列入等待名单，n-Lorem将很快开始对第40位患者进行治疗。

But at the time the Rosens learned about the work that Crooke was doing, n-Lorem was just getting started. Chung submitted an application for n-Lorem to develop a treatment for Susannah, and Susannah became n-Lorem's first patient to be treated with an ASO therapy developed by the foundation.

但是，当罗森夫妇了解到克鲁克正在进行的工作时，n-Lorem才刚刚起步。钟提交了申请，希望n-Lorem为苏珊娜开发一种治疗方法，苏珊娜成为n-Lorem第一个接受该基金会开发的ASO疗法的患者。

ASO therapy is a spinal procedure that pulls out fluid and replaces it with the drug that targets the gene mutation. In Susannah's case, the ASO therapy allows for normal protein production.

ASO疗法是一种脊髓手术，可以抽出液体并用针对基因突变的药物替代。在苏珊娜的案例中，ASO疗法使得正常蛋白质的生产成为可能。

Sally Jackson and her daughter, Susannah Rosen, in a hospital bed

萨莉·杰克逊和她的女儿苏珊娜·罗森在医院的病床上

Courtesy: The Rosen Family

Courtesy: 罗森家族

'It's genetic medicine,' Crooke said. 'So we take the genetic code directly and design a relatively small molecule, 18 to 20 genetic letters with that genetic 'ZIP code' that will direct it to the RNA in the cell that we want it to bind to. And then we can design the ASO to do various things: to prevent the production of a disease-causing protein, produce a better protein, or produce a protein that's not being produced in enough quantity.'.

“这是基因药物，”克鲁克说。“所以我们直接采用基因代码并设计一个相对较小的分子，这个分子有18到20个基因字母和那个基因‘邮政编码’，会引导它结合到我们希望它结合的细胞中的RNA上。然后我们可以设计反义寡核苷酸（ASO）来做各种事情：防止产生致病蛋白、生产更好的蛋白质，或生产那些产量不足的蛋白质。”

After Susannah's second dose, Luke started noticing a difference in Susannah's behavior, he said.

卢克说，在苏珊娜第二次服药后，他开始注意到苏珊娜的行为有所不同。

'One morning after she had received treatment, we were sitting at breakfast, and I was like, 'Something is wrong,'' Luke recalled. 'But it wasn't. It was the fact that it was quiet and we were able to look at each other. Her tremor was gone. That's not an FDA-approved outcome measure or an end point, but it is something that just means the world to us.

“有一天早上，在她接受治疗后，我们正坐着吃早餐，我当时觉得‘有点不对劲’，”卢克回忆道。“但其实没有问题。只是因为周围很安静，我们能够彼此对视。她的震颤消失了。这不是美国食品药品监督管理局批准的疗效指标或终点，但对我们来说却意义非凡。”

She still has her challenges and problems, but just that tremor going away, where we can have breakfast together ... that's when I knew that the drug was working.'.

她仍然面临挑战和问题，但仅仅是震颤消失了，我们能一起吃早餐……那时我就知道药物起作用了。

The Rosen family enjoy a meal together.

罗森一家一起享用了一顿饭。

Courtesy: The Rosen Family

Courtesy: 罗森家族

Susannah's been receiving the ASO treatments for three years, and the Rosens said they're thankful for the time it's given them. But they know the road ahead for Susannah will likely remain a difficult one.

苏珊娜已经接受了三年的ASO治疗，罗森夫妇说他们很感激这段时间。但他们知道，苏珊娜未来的道路可能仍然艰难。

'We're afraid the disease is catching up to the treatment. She's regressing in ways — and we just wish we had gotten this treatment for her five years ago,' Luke said. 'The next kiddo [to receive the same treatment] will be younger, and the treatment will get into every brain cell ... I know it. Our gal is a pioneer.

“我们担心疾病正在赶上治疗的步伐。她在某些方面正在退步——我们只希望五年前就能为她提供这种治疗，”卢克说。“下一个接受相同治疗的孩子会更年轻，治疗将能够进入每个脑细胞……我知道会的。我们的女孩是个先驱。”

It's both heartbreaking and in part heartwarming. She's amazing and tough as nails.'.

这既令人心碎，又在某种程度上令人心暖。她非常了不起，坚韧不拔。

To learn more about KIF1A-associated neurological disorders, see Luke and Sally's foundation,

要了解更多关于KIF1A相关神经系统疾病的信息，请参阅Luke和Sally的基金会，

KIF1A.org

KIF1A.org

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