Alzheimer’s Breaks Through. Parkinson’s Plays Catch-Up.
阿尔茨海默病取得突破 帕金森病迎头赶上
by Tan Weiyun 作者：谭伟云
[Biopharma] [生物制药]
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Alzheimer’s has finally crossed into the era of disease-modifying treatment. Parkinson’s is still waiting for its breakthrough.阿尔茨海默病终于迈入了疾病修饰治疗时代。帕金森病仍在等待其突破性进展。
The arrival of disease-modifying drugs that can clear amyloid plaques has pushed Alzheimer’s into a new phase, where the race is moving toward earlier diagnosis and earlier treatment.能够清除淀粉样蛋白斑块的疾病修饰药物的问世，将阿尔茨海默病推向了一个新阶段，这场竞争正朝着早期诊断和早期治疗的方向发展。
“We can now talk about prevention,” Jeffrey Cummings, a leading Alzheimer’s researcher, told a brain diseases conference at the World Laureates Forum in Shanghai.“我们现在可以谈谈预防了，”顶尖阿尔茨海默病研究专家杰弗里·卡明斯在上海世界顶尖科学家论坛的一场脑部疾病会议上表示。
Parkinson’s remains on the other side of that divide. Existing drugs largely control symptoms, while researchers are still hunting for reliable biomarkers, better targets and the first treatment that can slow the disease itself. The pressure is rising fast: Nobel laureate Randy Schekman said Parkinson’s is growing faster than any other neurodegenerative disease and could affect close to 20 million people over the next 10 to 20 years, with China accounting for more than half of new cases over the coming decade.帕金森病仍处于这一鸿沟的另一侧。现有药物主要只能控制症状，而研究人员仍在寻找可靠的生物标志物、更有效的作用靶点，以及首款能够延缓疾病本身进展的治疗方法。压力正迅速攀升：诺贝尔奖得主兰迪·谢克曼表示，帕金森病的增长速度超过其他任何神经退行性疾病，未来10至20年可能影响近2000万人，而未来十年新增病例中中国占比超过一半。
For Alzheimer’s, the breakthrough was not a cure. But it proved that the course of the disease could be changed.对于阿尔茨海默病而言，这次突破并非找到了治愈方法。但它证明了这种疾病的病程是可以被改变的。
Anti-amyloid drugs such as lecanemab and donanemab can remove plaques from the brain and slow cognitive decline in some patients with early Alzheimer’s. They also come with limits, including modest clinical benefits and the risk of brain swelling or bleeding. Still, their arrival broke a decades-long run of failures and gave drugmakers something the field had lacked: proof that targeting the biology behind the disease could work.仑卡奈单抗、多奈哌单抗等抗淀粉样蛋白药物能够清除部分早期阿尔茨海默病患者大脑中的斑块，并减缓其认知衰退。这类药物也存在局限性，包括临床疗效有限以及存在脑肿胀或出血的风险。不过，它们的问世打破了数十年来的研发失败僵局，也为制药行业带来了此前一直缺失的东西：证明针对该疾病背后的生物学机制进行干预是可行的。
That has pushed the race earlier. 这让这场研发竞赛提前开启。
Alzheimer’s can begin in the brain about 15 years before symptoms emerge, Cummings said. New blood tests can now help identify signs of the disease without sending every patient for an expensive PET scan, opening the door to much broader screening.卡明斯表示，阿尔茨海默病的症状出现前约15年，该病就可能已在大脑中发作。如今新的血液检测可帮助识别该病的相关迹象，无需让所有患者都接受昂贵的PET扫描，这为更广泛的筛查打开了大门。
“These tools are something we could not have imagined before,” he said.“这些工具是我们以前无法想象的，”他说。
The impact could reach well beyond diagnosis. Cummings said 20 to 30 percent of participants entering Alzheimer’s clinical trials have in the past turned out not to have amyloid in their brains, meaning some patients may have been enrolled in trials for drugs that could never have helped them. Easier blood testing could make trials faster, cheaper and more selective.这一影响可能远超诊断环节。卡明斯表示，过去参与阿尔茨海默病临床试验的受试者中，有20%至30%最终被证实大脑中不存在淀粉样蛋白，这意味着部分患者可能入组了针对那些根本无法对其产生疗效的药物的试验。更便捷的血液检测能让临床试验更快、成本更低，且筛选更精准。
Parkinson’s does not yet have the same advantage.帕金森病目前还没有这一优势。
One of its hallmark proteins, alpha-synuclein, forms abnormal deposits in the brain, but researchers still lack a widely available way to see those deposits in living patients. Schekman said researchers currently rely heavily on cell models and tissue from patients after death, although new PET tracers under development could eventually change that.其标志性蛋白之一α-突触核蛋白会在大脑中形成异常沉积，但研究人员目前仍缺乏一种可广泛应用的方法来检测活体患者体内的这种沉积。谢克曼表示，尽管目前有新的PET示踪剂处于研发阶段，最终可能改变这一现状，但研究人员当前仍高度依赖细胞模型以及患者死后的组织样本。
That leaves Parkinson’s drug developers fighting on two fronts: finding a treatment that can alter the disease, and building better tools to tell whether it is working.这使得帕金森病药物研发者陷入两线作战的困境：既要找到能够改变疾病进程的治疗方法，又要研发更先进的工具来判断治疗是否有效。
The problem is not a shortage of ideas.问题不在于缺乏思路。
Researchers at the Shanghai meeting pointed to alpha-synuclein, damaged mitochondria and genetic pathways such as PINK1 and Parkin as possible routes into the disease. But most remain far from producing a medicine that changes the course of Parkinson’s.上海会议的研究人员指出，α-突触核蛋白、受损的线粒体以及PINK1和Parkin等基因通路可能是引发该疾病的潜在途径。但目前，大多数研究仍远未研发出能够改变帕金森病病程的药物。
Some of the most obvious bets have already disappointed. Schekman pointed to an antibody designed to block the spread of alpha-synuclein that failed to slow disease progression in a clinical trial. “The trial was not successful,” he said.一些最显而易见的研究方向已经让人失望。谢克曼指出，一种旨在阻断α-突触核蛋白传播的抗体在临床试验中未能减缓疾病进展。“这项试验没有取得成功，”他说。
That failure also shows why simply copying the Alzheimer’s playbook may not work. In Alzheimer’s, antibodies that target amyloid outside cells have delivered measurable benefits. Schekman said alpha-synuclein may spread between brain cells in ways that are harder for antibodies to reach, forcing researchers to rethink how, and where, to attack the disease.这一失败也表明，为何简单照搬阿尔茨海默病的治疗方案可能行不通。在阿尔茨海默病的治疗中，靶向细胞外淀粉样蛋白的抗体已带来了可衡量的疗效。谢克曼表示，α-突触核蛋白可能以抗体更难触及的方式在脑细胞间传播，这迫使研究人员重新思考攻击该疾病的方式与靶点。
For now, much of that work remains upstream of drug development.目前，这类研究大多还处于药物研发的上游阶段。
Schekman leads the Aligning Science Across Parkinson’s initiative, or ASAP, which brings together research teams from around the world to study the basic biology of Parkinson’s. Its goal, he said, is not to develop drugs or run clinical trials itself, but to generate findings that biotech and pharmaceutical companies can take forward.谢克曼领导着“帕金森病科学协同计划”（简称ASAP），该计划汇集了来自全球各地的研究团队，共同研究帕金森病的基础生物学机制。他表示，该计划的目标并非亲自研发药物或开展临床试验，而是产出可供生物技术和制药公司进一步推进的研究成果。
The ambition is less dramatic than a cure, but potentially more realistic.这一目标虽不如治愈疾病那般轰动，却可能更具现实可行性。
“Our goal is to make Parkinson’s a disease that can be controlled like diabetes,” Schekman said.“我们的目标是让帕金森病成为一种像糖尿病那样可以控制的疾病，”谢克曼说。
Getting there will require what Alzheimer’s has only recently achieved: turning a growing understanding of disease biology into treatments that can show, in patients, that they actually change what comes next.要实现这一目标，需要做到阿尔茨海默病领域近期才达成的事：将对疾病生物学日益深入的理解，转化为能够在患者身上证明其确实能改变疾病发展进程的疗法。
China is likely to be central to that effort. If Schekman’s projection holds, the country will account for more than half of the world’s new Parkinson’s cases over the next decade, creating both a growing treatment burden and a much larger base for clinical research.中国很可能是这一工作的核心。如果谢克曼的预测准确，未来十年中国将占全球新增帕金森病病例的一半以上，这既会带来日益加重的治疗负担，也会为临床研究奠定规模大得多的基础。
For drugmakers, that raises the stakes. Alzheimer’s has shown that decades of basic science can eventually produce medicines that alter disease. Parkinson’s now has to prove it can do the same.对于制药公司而言，这大大增加了风险。阿尔茨海默病的案例表明，数十年的基础科学研究最终能够研发出改变疾病进程的药物。帕金森病如今则必须证明自己也能做到这一点。
Editor: Yao Minji 编辑：姚敏吉
