Alzheimer’s Breaks Through. Parkinson’s Plays Catch-Up.
阿爾茨海默病取得突破 帕金森病迎頭趕上
by Tan Weiyun 作者：譚偉雲
[Biopharma] [生物製藥]
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Alzheimer’s has finally crossed into the era of disease-modifying treatment. Parkinson’s is still waiting for its breakthrough.阿爾茨海默病終於邁入了疾病修飾治療時代。帕金森病仍在等待其突破性進展。
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.能夠清除澱粉樣蛋白斑塊的疾病修飾藥物的問世，將阿爾茨海默病推向了一個新階段，這場競爭正朝着早期診斷和早期治療的方向發展。
“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.“我們現在可以談談預防了，”頂尖阿爾茨海默病研究專家傑弗裏·卡明斯在上海世界頂尖科學家論壇的一場腦部疾病會議上表示。
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.帕金森病仍處於這一鴻溝的另一側。現有藥物主要只能控制症狀，而研究人員仍在尋找可靠的生物標誌物、更有效的作用靶點，以及首款能夠延緩疾病本身進展的治療方法。壓力正迅速攀升：諾貝爾獎得主蘭迪·謝克曼表示，帕金森病的增長速度超過其他任何神經退行性疾病，未來10至20年可能影響近2000萬人，而未來十年新增病例中中國佔比超過一半。
For Alzheimer’s, the breakthrough was not a cure. But it proved that the course of the disease could be changed.對於阿爾茨海默病而言，這次突破並非找到了治癒方法。但它證明了這種疾病的病程是可以被改變的。
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.侖卡奈單抗、多奈哌單抗等抗澱粉樣蛋白藥物能夠清除部分早期阿爾茨海默病患者大腦中的斑塊，並減緩其認知衰退。這類藥物也存在侷限性，包括臨牀療效有限以及存在腦腫脹或出血的風險。不過，它們的問世打破了數十年來的研發失敗僵局，也爲製藥行業帶來了此前一直缺失的東西：證明針對該疾病背後的生物學機制進行干預是可行的。
That has pushed the race earlier. 這讓這場研發競賽提前開啓。
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，阿爾茨海默病的症狀出現前約15年，該病就可能已在大腦中發作。如今新的血液檢測可幫助識別該病的相關跡象，無需讓所有患者都接受昂貴的PET掃描，這爲更廣泛的篩查打開了大門。
“These tools are something we could not have imagined before,” he said.“這些工具是我們以前無法想像的，”他說。
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.這一影響可能遠超診斷環節。卡明斯表示，過去參與阿爾茨海默病臨牀試驗的受試者中，有20%至30%最終被證實大腦中不存在澱粉樣蛋白，這意味着部分患者可能入組了針對那些根本無法對其產生療效的藥物的試驗。更便捷的血液檢測能讓臨牀試驗更快、成本更低，且篩選更精準。
Parkinson’s does not yet have the same advantage.帕金森病目前還沒有這一優勢。
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.其標誌性蛋白之一α-突觸核蛋白會在大腦中形成異常沉積，但研究人員目前仍缺乏一種可廣泛應用的方法來檢測活體患者體內的這種沉積。謝克曼表示，儘管目前有新的PET示蹤劑處於研發階段，最終可能改變這一現狀，但研究人員當前仍高度依賴細胞模型以及患者死後的組織樣本。
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.這使得帕金森病藥物研發者陷入兩線作戰的困境：既要找到能夠改變疾病進程的治療方法，又要研發更先進的工具來判斷治療是否有效。
The problem is not a shortage of ideas.問題不在於缺乏思路。
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.上海會議的研究人員指出，α-突觸核蛋白、受損的線粒體以及PINK1和Parkin等基因通路可能是引發該疾病的潛在途徑。但目前，大多數研究仍遠未研發出能夠改變帕金森病病程的藥物。
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.一些最顯而易見的研究方向已經讓人失望。謝克曼指出，一種旨在阻斷α-突觸核蛋白傳播的抗體在臨牀試驗中未能減緩疾病進展。“這項試驗沒有取得成功，”他說。
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.這一失敗也表明，爲何簡單照搬阿爾茨海默病的治療方案可能行不通。在阿爾茨海默病的治療中，靶向細胞外澱粉樣蛋白的抗體已帶來了可衡量的療效。謝克曼表示，α-突觸核蛋白可能以抗體更難觸及的方式在腦細胞間傳播，這迫使研究人員重新思考攻擊該疾病的方式與靶點。
For now, much of that work remains upstream of drug development.目前，這類研究大多還處於藥物研發的上游階段。
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.謝克曼領導着“帕金森病科學協同計劃”（簡稱ASAP），該計劃彙集了來自全球各地的研究團隊，共同研究帕金森病的基礎生物學機制。他表示，該計劃的目標並非親自研發藥物或開展臨牀試驗，而是產出可供生物技術和製藥公司進一步推進的研究成果。
The ambition is less dramatic than a cure, but potentially more realistic.這一目標雖不如治癒疾病那般轟動，卻可能更具現實可行性。
“Our goal is to make Parkinson’s a disease that can be controlled like diabetes,” Schekman said.“我們的目標是讓帕金森病成爲一種像糖尿病那樣可以控制的疾病，”謝克曼說。
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.要實現這一目標，需要做到阿爾茨海默病領域近期才達成的事：將對疾病生物學日益深入的理解，轉化爲能夠在患者身上證明其確實能改變疾病發展進程的療法。
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.中國很可能是這一工作的核心。如果謝克曼的預測準確，未來十年中國將佔全球新增帕金森病病例的一半以上，這既會帶來日益加重的治療負擔，也會爲臨牀研究奠定規模大得多的基礎。
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.對於製藥公司而言，這大大增加了風險。阿爾茨海默病的案例表明，數十年的基礎科學研究最終能夠研發出改變疾病進程的藥物。帕金森病如今則必須證明自己也能做到這一點。
Editor: Yao Minji 編輯：姚敏吉
