格伦（左起）、贝克汉姆、卡拉和伊莱扎·奥尼尔于2015年拍摄全家福。伊莱扎患有圣菲利波综合征，这是一种罕见的遗传性疾病。
Glenn (from left), Beckham, Cara and Eliza O'Neill pose for a family photo in 2015. Eliza has Sanfilippo syndrome, a rare inherited disease.
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在伊莱扎·奥尼尔（Eliza O'Neill）小的时候，她是那种总是需要带个配饰（比如帽子或围巾）的孩子。
When Eliza O'Neill was little, she was one of those kids who always needed to have an accessory, like a hat or a scarf.
“她总是去衣柜里拿我的高跟鞋，然后踩着它们哒哒哒地走——这把我们吓得要命，”南卡罗来纳州哥伦比亚市的儿科医生、她的母亲卡拉·奥尼尔（Cara O'Neill）说。
"She would always go get my high heels from the closet and clop around in those — which she scared us to death," says her mom, Cara O'Neill, a pediatrician in Columbia, S.C.
但就在伊莱扎快满3岁时，她的父母发现她在发育里程碑上落后了。她被诊断出患有语用性语言发育迟缓，这意味着她虽然学了很多词，但在社交场合中并没有以典型的方式使用它们。
But by the time Eliza turned 3, her parents noticed she was falling behind on developmental milestones. She was diagnosed with a pragmatic speech delay, meaning she had learned a lot of words, for example, but she wasn't using them in a typical way in social situations.
2013年，卡拉的一位同事建议对伊莱扎进行一组代谢障碍筛查——这只是为了排除这些疾病。
In 2013, one of Cara's colleagues suggested testing Eliza for a group of metabolic disorders — just to rule them out.
但检测结果呈阳性，显示她患有一种名为圣菲利波综合征的疾病。卡拉记起自己在医学院时曾学过这种罕见的遗传疾病。
But the test came back positive for something called Sanfilippo syndrome Cara remembered learning about the rare inherited disease back in medical school.
“当他们说出这个词时，记忆一下子全都涌了上来，”她说。“那种恐惧感就像压舱石一样压在心头，天哪，这太可怕了。”患有圣菲利波综合征的孩子体内有一个缺陷基因，导致他们无法分解硫酸肝素，而这种分子对正常的细胞功能至关重要。随着它在体内积聚，会引起严重的并发症。
"When they said the word, it all kind of came rushing back," she says. "And it was just this bale of dread, like, oh, my goodness, this is horrific." Children with Sanfilippo have a faulty gene that leaves them unable to break down heparin sulfate, a molecule critical to normal cell function. As it builds up in the body, it causes severe complications.
据奥尼尔夫妇创立并持续运营的“治愈圣菲利波基金会”称，患有该综合征的孩子会失去说话和走路的能力。他们会癫痫发作，通常活不过十几岁。
Kids with Sanfilippo lose their ability to speak and walk. They have seizures, and they usually don't live past their teens, according to the Cure Sanfilippo Foundation which the O'Neills started and continue to run.
对于伊莱扎的父亲格伦·奥尼尔（Glenn O'Neill）来说，在得知伊莱扎的检测结果后，过了好一会儿，诊断结果带来的打击才真正沉淀下来。
For Eliza's dad, Glenn O'Neill, it took a little while after learning Eliza's test results for the diagnosis to sink in.
“直到我回到家，我才真正意识到这种退化发生得有多快，”他说。“也就是在那个时候，我们说：‘天哪。无论我们需要做什么，我们现在就要去做。’” 研究治疗方法 在俄亥俄州哥伦布市的全国儿童医院，研究员付海燕（音）自20世纪90年代末以来一直在研究针对小鼠圣菲利波综合征的基因疗法。
"It wasn't really until I got home that I realized how quickly the degeneration happened," he says. "And that was really the point where we said, 'Gosh. Whatever we need to do, we need to do it now.'" Researching a treatment At Nationwide Children's Hospital in Columbus, Ohio, researcher Haiyan Fu had been working on a gene therapy in mice for Sanfilippo since the late-1990s.
该疗法利用改造后的病毒将缺陷基因的工作副本输送到患者细胞中。
rapy used a modified virus to deliver a working copy of the broken gene to patients' cells.
在2016年成为首个接受罕见病实验性基因疗法的人之前，伊莱扎·奥尼尔得到了父亲格伦的亲吻。
Eliza O'Neill gets a kiss from her dad, Glenn, before becoming the first person to receive an experimental gene therapy for her rare disease in 2016.
奥尼尔家庭 付海燕意识到这项实验性疗法很有前景。“如果我们尽早治疗，它甚至可能成为一种治愈方法，”她说。“所以我不能放弃。” 不过，维持这项研究并为其提供资金充满挑战。她曾以为自己不得不在2009年辞职。但圣菲利波患儿的家属们拦住了她。
O'Neill family Fu realized the experimental therapy was promising. "And if we treat early, it could be potentially a cure," she says. "So I can't give up." Keeping it going – and funded – was challenging, though. She thought she would have to quit in 2009. But the families of kids with Sanfilippo stopped her.
“他们说：‘你不能离开。我们可以给你提供一些资金，让你，你知道的，继续做下去吗？’”付海燕回忆说，并解释说这些家庭从一开始就一直在帮助她，不希望看到她的研究中断。
"They said, 'You can't leave. Can we give you some of the funds for you to, you know, carry on?'" Fu recalls, explaining that these families had helped her from the beginning and didn't want to see her work stop.
总共有八个患者基金会（包括“本的梦想”和“治愈柯比”），让付海燕的研究得以继续，直至该研究准备好进行首个临床人体试验。
In all, eight patient foundations, including Ben's Dream and a Cure for Kirby kept Fu's work going until the research was ready for the first human trial.
筹集资金 但临床试验的费用将会非常昂贵。格伦·奥尼尔对如何筹集资金产生了一个想法。
Raising the money But a clinical trial would be expensive. Glenn O'Neill had an idea for how to raise the money.
“我们突发奇想，在网上联系了一些素不相识的人，想制作一个病毒式传播的视频，”他说，他指的是电影制作人本杰明·冯·黄（Benjamin Von Wong），后者在2014年的几天里为他们制作了一个视频。这成功了。
"We reached out on a whim to some strangers that we found on the internet about making a viral video," he says, referring to filmmaker Benjamin Von Wong, who made them a video over a few days in 2014. It worked.
2014年春天，“拯救伊莱扎”视频帮助奥尼尔夫妇打破了GoFundMe当时的纪录，在短短几周内筹集了100万美元。不久之后，筹款额达到了200万美元。
In the spring of 2014, the Saving Eliza video helped the O'Neills break GoFundMe's record at the time, raising a million dollars in just a few weeks. Soon, it hit $2 million.
筹集的资金帮助资助了首个临床人体试验，该试验于2016年5月启动。这些实验展现出了足够广阔的前景，引起了生物技术行业的注意。
The money raised helped fund the first human trial, which started in May 2016. The experiments were promising enough for the biotech industry to take notice.
最终，一家名为Ultragenyx的生物技术公司于2022年收购了该基因疗法的权益并继续进行研究。几年后，该公司向食品药品监督管理局提交了数据以供审评。
Ultimately, a biotech company called Ultragenyx acquired the rights to the gene therapy in 2022 and kept studying it. A few years later, the company submitted data to the Food and Drug Administration for review.
食药局于9月批准了该基因疗法。这种单次输注药物被称为Fayuvi。
FDA approved the gene therapy in September. The one-time infusion is called Fayuvi.
“孩子的年龄越小，治疗效果就越好，因为大脑保留得越多，”Ultragenyx公司首席执行官埃米尔·卡基斯（Emil Kakkis）说。“等他们到2岁、3岁或4岁被诊断并弄清楚病情时，他们已经失去了很多机会。我们治疗过几个6个月大的孩子，他们的效果非常好。我们的观点是，当你对他们进行极早的治疗时，实际上能获得更好的基因疗法效果。” 药物价格研究公司46brooklyn的数据显示，Ultragenyx将该疗法的定价定在近400万美元，并列为有史以来第二昂贵的基因疗法。
"The treatment will work best the younger the child is because the more brain is remaining," says Ultragenyx CEO Emil Kakkis. "By the time they're 2 or 3 or 4 years old diagnosed, getting figured out, they've lost a lot of ground. And we have treated a few kids that were in the 6-month age that have done really well. And our view is that when you treat them really young, you actually get better gene therapy results." Ultragenyx set the price for the treatment at nearly $4 million, tying it for the second most expensive gene therapy ever, according to 46brooklyn a drug price research firm.
卡基斯表示，Ultragenyx致力于确保每一位患者都能得到治疗，无论价格如何。“不应该有任何后勤、地点、地区或州的限制或其他类型的规定来阻止我们为患者提供治疗。我们明白我们必须做什么。” 食药局宣布批准该消息几分钟后，付海燕接到了卡拉·奥尼尔的电话，并收到了其他资助她研究的家庭发来的信息。其中一些人在这个过程中失去了孩子。
Kakkis says Ultragenyx is committed to making sure every patient is treated, regardless of the price. "There should be no logistical location, site or state or other kind of rule that stops us from getting the patient treated. We understand what [we've] got to do." Moments after the FDA approval was announced, Fu got a call from Cara O'Neill — and messages from other families that funded her research. Some had lost a child along the way.
付海燕表示，Fayuvi获批是个好消息，但这给她带来了复杂的情绪：“本不该花这么长时间。” 至于伊莱扎，她现在快17岁了。早在2016年，她作为临床试验的一部分，接受了该基因疗法，成为了第一位患者。
Fu says Fayuvi's approval is good news, but it brings mixed emotions for her: "It shouldn't take this long." As for Eliza, she's almost 17 now. She was the very first patient to get the gene therapy as part of a clinical trial back in 2016.
由于她在接受基因疗法时已经6岁，她当时已经失去了说话的能力。这种能力再也没有恢复，但她可以通过图片卡和设备进行交流。伊莱扎在上学。今年夏天，她游泳并学会了在泳池浮条上漂浮。
Because she was 6 years old when she was treated with the gene therapy, she had already lost her ability to speak. It never returned, but she can communicate with picture cards and devices. Eliza goes to school. And this summer, she swam and learned to float on a pool noodle.
“我只是为我的女孩感到骄傲。你知道吗？”格伦·奥尼尔说。“我为她感到骄傲。对她来说这是一条艰难的路，但我们也知道她非常幸运。”
"I just feel proud of my girl. You know?" Glenn O'Neill says. "I feel proud of her. It's been a rough road for her, but we also know she's very lucky."