对于绝大多数囊性纤维化患者来说，新药物彻底改变了他们的生活——原本令人痛苦不堪的肺部疾病如今已变得可控。
For the vast majority of cystic fibrosis patients, new drugs have been life-changing, transforming a debilitating lung disease into a manageable condition.
然而，约有10%的患者因携带其他基因突变，这些疗法对他们无效。
But for about 10% of patients born with other genetic mutations, these treatments don't work.
“我们被遗忘了，”艾米丽·克莱默-戈林科夫说道。她创办了非营利组织“艾米丽的伙伴团”，旨在加速针对那些对现有疗法无反应或出现副作用的“最后10%”囊性纤维化患者的研究工作。
"We have been left behind," said Emily Kramer-Golinkoff, who founded a nonprofit, Emily's Entourage, to speed up research for what she calls "the final 10%" of CF patients who don't respond to the current treatments or experience side effects.
本周，全球囊性纤维化患者群体齐聚亚特兰大参加年度盛会。克莱默-戈林科夫希望这些患者能成为讨论的核心，尤其是在近期科研遭遇挫折的背景下。今年5月，Vertex制药公司与Moderna公司因耐受性问题，中止了一项利用mRNA技术治疗上述10%患者的临床试验——该技术正是新冠疫苗的研发基础。今年2月，勃林格殷格翰公司也终止了一项针对囊性纤维化的基因疗法试验。
As the cystic fibrosis community gathers this week in Atlanta for its largest annual gathering, Kramer-Golinkoff is hoping those patients will be a big part of the conversation, particularly after recent scientific setbacks. In May, Vertex and Moderna stopped a clinical trial of a drug that used mRNA, the technology behind the Covid vaccines, to treat those CF patients in the 10%, citing tolerability issues. In February, the drugmaker Boehringer Ingelheim ended a trial of a gene therapy for CF.
40多年前，年仅6周大的克莱默-戈林科夫被确诊患有这种致命的遗传性疾病。在那个年代，一次临床试验失败便意味着生命的终结。但如今，得益于她所创办的非营利组织的努力，希望之光已然出现。
Over four decades ago, when Kramer-Golinkoff was diagnosed with the progressive and fatal genetic disease at six weeks old, a failed clinical trial would have been where the story ends. But today, thanks largely to her nonprofit's work, there are rays of hope.
囊性纤维化影响着约4万名美国人，该病会导致浓稠黏性的黏液在肺部堆积，进而引发危及生命的肺部感染与呼吸衰竭。约90%的患者携带特定基因突变，能够从Vertex制药公司生产的Trikafta及升级版药物Alyftrek中获益。这两种药物通过改善CFTR蛋白的功能来调节体内的盐分与水分平衡，从而稀释患者肺部的黏液。《大西洋月刊》2024年刊发的一篇文章以“彻底改变一切的囊性纤维化治疗突破”为题，详细描述了这些患者如今已能够轻松跑上楼梯，甚至参加10公里赛跑。
Affecting about 40,000 Americans, cystic fibrosis causes thick, sticky mucus to build up in the lungs, creating life-threatening lung infections and respiratory failure. About 90% of patients with the disease have a certain genetic mutation and can benefit from Trikafta and a newer-version, Alyftrek, which are both made by Vertex Pharmaceuticals. By improving the function of a protein called CFTR that maintains the balance of salt and water in the body, the drugs thin the mucus in a patient's lungs. A 2024 article in The Atlantic, headlined "The Cystic-Fibrosis Breakthrough That Changed Everything," described how those patients can now run up stairs and take part in 1o-K races.
不过，对于像克莱默-戈林科夫这样无法产生具有正常功能的CFTR蛋白、因而无法从这些药物中获益的患者来说，这一重大突破并未带来多大改变。
But for patients like Kramer-Golinkoff who don't produce a fully functional CFTR protein to benefit from those drugs, the big breakthrough didn't change much.
自2011年创立以来，艾米丽援助基金会已筹集超过2200万美元，资助了51个研究项目，致力于开发多种治疗手段，包括反义寡核苷酸疗法、小分子药物以及基因疗法。
Since its creation in 2011, Emily's Entourage has raised more than $22 million and funded 51 research projects developing multiple therapeutic approaches, including antisense oligonucleotides, or ASOs, small molecules and gene therapies.
将药物精准递送到目标细胞是一项极具挑战性的科学难题，因为肺部本就是一个用来阻挡外界物质进入的器官。更棘手的是，囊性纤维化患者的肺部还充满了黏液。
Delivering a drug to the right cells presents an especially difficult scientific problem because the lung is an organ designed to keep things out. Adding to that challenge, the lung of a CF patient is filled with mucus.
“在健康的肺部中，这已经是个极其艰巨的任务，”艾米丽援助基金会首席科学官钱德拉巴利·戈斯说道，“而在囊性纤维化患者的肺部，难度更是呈指数级上升。”斯皮罗万特科学公司研发的一种颇具前景的基因疗法有望适用于所有患者，无论其基因突变类型如何。目前该药物正处于早期临床试验阶段。
"It's incredibly challenging in a healthy lung," said Chandrabali Ghose, chief scientific officer for Emily's Entourage. "But it's orders of magnitude more difficult in a CF lung." One promising gene therapy developed by Spirovant Sciences could work regardless of a patient's genetic mutation. The drug is now in an early-stage clinical trial.
艾米丽援助基金会还在投入资金研究其他疗法：比如能杀灭细菌的天然噬菌体以及抗菌剂，这些手段可用于治疗那些对普通药物产生抗药性、甚至可能致命的感染。“我们认为这些疗法能起到争取时间的作用，”戈斯说道。
Emily's Entourage is also investing in other approaches — phages, which are naturally occurring viruses that kill bacteria, and antimicrobials – that treat drug-resistant infections that can ultimately be fatal for CF patients. "We see these as buying-time initiatives," Ghose said.
该基金会的工作最终或许还能帮助其他疾病患者，包括患有关节或皮肤感染的人群。该基金会还资助有关“无义突变”的研究——这种DNA变异会导致细胞提前停止蛋白质合成，进而引发疾病。科学家们从这些研究中获得的成果，也可能对各类罕见遗传病患者有所助益。
The foundation's work could ultimately help patients with other conditions, including people who suffer from joint and skin infections. Her group is also funding research into nonsense mutations, which are changes in DNA that cause the cells to stop making proteins earlier than they should, causing diseases. What scientists learn from that research could be relevant to patients with a range of rare genetic conditions.
“只要能取得突破性进展，我们所有人都能从中受益，”克莱默-戈林科夫说道。
"We all benefit when there's a leap forward," Kramer-Golinkoff said.
许多人听说囊性纤维化患者中有90%的病情已得到控制，便以为我们已经攻克了这种疾病，但事实并非如此。剩下的10%患者仍在与这种长期威胁生命的顽疾抗争。
Many people hear about the progress for 90% of the CF community and think we've figured it out, but that is not true. Those in the final 10% are still contending with the same killer disease that CF has always been."
“艾米丽·克莱默-戈林科夫，《艾米丽的伙伴》创始人：克莱默-戈林科夫从小KJ的故事中看到了希望。这个案例促使相关监管机构做出改革，允许科学家为每位患者量身定制药物。目前已知约有2000种基因突变可引发囊性纤维化，其中许多极为罕见，仅影响极少数人。
Emily Kramer-GolinkoffEmily's Entourage Founder Kramer-Golinkoff sees hope in the story of Baby KJ, which has spurred regulatory changes aimed at allowing scientists to develop custom-made drugs for individual patients. There are about 2,000 genetic mutations that cause cystic fibrosis. Many are extremely rare, affecting just a small handful of people.
她面临的最大挑战或许是纠正一种错误观念——即认为囊性纤维化已被治愈。这种误解严重阻碍了新疗法的研发投资。
Perhaps her biggest challenge is combating the misconception that cystic fibrosis has been cured, which stifles investment into new treatments.
现年41岁的克莱默-戈林科夫庆幸自己还活着。同龄的多数囊性纤维化患者要么已经离世，要么接受了肺移植手术。但她的日子也并不轻松：为控制肺部慢性感染需服用抗生素，全天候吸氧，还要注射多种胰岛素以治疗与该病相关的糖尿病，另外每天需服用30多粒药片——这一切都是为了保住仅存的肺功能并延缓病情恶化。
Now 41, Kramer-Golinkoff is grateful to be alive. Most CF patients at her stage are dying or receive lung transplants. But her life isn't easy. She's on antibiotics to control chronic infections in her lungs, takes supplemental oxygen around the clock, injects multiple shots for diabetes that's related to CF, and takes over 30 pills — all to salvage what lung function she has left and delay progression of the disease.
她深知自己并非个例，也明白绝不能忽视那些仍在等待突破性疗法的患者群体。“和我情况相同的人还有很多，”她说，“我们等不起啊。”
She knows she's not unique, and that it's important not to forget this group of patients who are still waiting for their big medical breakthrough. "There are a lot of other people in the same boat as me," she said. "We don't have time to wait."