Alzheimer's disease vaccine(Axon Biochemicals BV)

Axon Neuroscience's active tau immunotherapy AADvac1 has been selected as the first tau-targeted therapy to enter a groundbreaking U.S. Alzheimer's disease phase 2 clinical trial (supported by a USD 151 million grant) and, simultaneously, a new platform trial for progressive supranuclear palsy (PSP) (supported by a USD 75 million grant) SAN FRANCISCO, CA / ACCESS Newswire / February 4, 2026 / Axon Neuroscience, a global leader in immunotherapy for human neurodegenerative diseases with an internationally recognized scientific team, announces the achievement of two historic milestones with the potential to significantly influence the future treatment of Alzheimer's disease and progressive supranuclear palsy (PSP): 1. AADvac1 Selected as the First Tau Therapy in the Phase 2 Alzheimer's Tau Platform (ATP) Combination-Therapy Trial An independent panel of leading U.S. scientific and clinical experts selected AADvac1 as the first therapy targeting pathological tau protein to be evaluated in a clinical trial supported by a USD 151 million grant from the U.S. National Institutes of Health (NIH) . The study is led by Professor Adam Boxer of the University of California, San Francisco and Professor Keith Johnson of Harvard Medical School, Boston . The Alzheimer's Tau Platform (ATP) is the first clinical study to systematically combine therapies targeting the two main disease-driving proteins: amyloid and tau. This innovative platform design helps bring promising therapies to patients sooner, reduces the number of participants assigned to placebo, and allows new treatment options to be added quickly as evidence grows. AADvac1 will be evaluated as the first tau-directed regimen, with additional promising medicines to be added in the future. The Phase 2 trial aims to assess the safety and efficacy of AADvac1 both as a monotherapy and in combination with an approved anti-amyloid monoclonal antibody for Alzheimer's disease. Approximately up to 450 participants aged 50-80 with late preclinical or early prodromal Alzheimer's disease will be enrolled. 2. AADvac1 Also Selected for the New Platform Trial for Progressive Supranuclear Palsy (PSP) Progressive supranuclear palsy (PSP) is a rare and rapidly progressing neurodegenerative disease that typically leads to death within approximately seven years of symptom onset. There are currently no approved therapies capable of slowing disease progression. The new PSP Trial Platform (PTP), led by the University of California, San Francisco, will be conducted at 50 clinical centers across the U.S. and Canada. The study is similarly like the ATP designed as a long-term platform protocol evaluating multiple investigational therapies. The platform is funded by a five-year NIA/NIH grant of up to USD 75.4 million - one of the largest grants UCSF has ever received for rare neurodegenerative diseases. The initial phase of the platform will test three therapeutics; the first two selected regimens are AADvac1 and AZP2006/Ezeprogind from a French biotechnology company AlzProtect. A third regimen has been selected and will be announced in early 2026. Approximately 440 patients with PSP-Richardson syndrome are expected to be enrolled in all therapeutic arms. 3. Why is AADvac1 a strong Candidate: A Strong Clinical and Scientific Basis AADvac1 is an active immunotherapy that stimulates the body to generate antibodies against pathological forms of tau protein. In the completed 24-month Phase 2 ADAMANT clinical trial in Alzheimer's patients, AADvac1 demonstrated: a favorable safety profile, a strong immune response (most patients generated high levels of anti-tau antibodies), pronounced effects on blood and CSF biomarkers of neurodegeneration and neuroinflammation, supportive clinical effects indicating potential to slow the disease progression, particularly in patients with confirmed tau pathology. Results from AADvac1's multi-year development program have been published in leading scientific journals, including Nature Aging , Lancet Neurology , and others. A key recent post-hoc analysis published in Alzheimer’s Research & Therapy further strengthened the evidence that AADvac1 can modulate critical biological processes in Alzheimer's disease. Independent scientific and clinical expert groups in the U.S. have therefore selected AADvac1 as one of the first candidates for both platform trials: in ATP as the first tau-targeted regimen and the first active immunotherapy tested in combination with anti-amyloid antibody therapy, in the PSP Platform as one of the first two therapies evaluating the potential to slow brain-volume loss and clinical progression in PSP. 4. Global Recognition of Scientific Expertise Axon Neuroscience was founded in 1999 by a Slovak immunologist Professor Michal Novak, who was part of the MRC Laboratory of Molecular Biology team in Cambridge that identified tau protein as the main component of neurofibrillary pathology in Alzheimer's disease. For his lifelong contribution to research, he has received prestigious awards including the Alzheimer’s Association Lifetime Achievement Award (2021) and the WHO Prize for Research in Healthcare of the Elderly (2016). Axon Neuroscience, the company he founded: is among the pioneers of tau immunotherapy in Alzheimer's disease and related tauopathies, has conducted four clinical trials across eight European countries , was among the first to identify and validate the diagnostic potential of the blood biomarker pTau217 , now one of the principal biomarkers for blood-based Alzheimer's diagnostics, was highlighted by independent research led by Karolinska Institutet (2024), which concluded that AADvac1 is among the possible future Alzheimer’s therapies and particularly suitable for combination treatment with amyloid-targeting medicines, has in its pipeline a promising humanized antibody AADvac2 , whose mechanism of action has been indirectly validated by the AADvac1 clinical data and which may offer a more effective treatment for later disease stages or patients with weaker immune responses. 5. Prestigious Collaborations, European Grants, and Partnerships Axon Neuroscience has received two major Horizon 2020 - Marie Skłodowska-Curie Actions grants, among the prestigious European scientific funding schemes supporting excellent research and the mobility of top scientists. The company also maintains a long-term project partnership with the University of Cambridge , supported by the grants from UK Research and Innovation funding system . Axon further collaborates with leading global pharmaceutical and biotechnology companies on the development of therapeutics for neurodegenerative diseases. Executive and Scientific Leadership Quotes Norbert Zilka, DrSc., Chief Scientific Officer: "The selection of AADvac1 for two independent NIA/NIH-funded platform trials led by prestigious U.S. academic centers is a strong confirmation of the high standard of our clinical research. The active tau immunotherapy we have been developing for more than a decade is now rightfully at the forefront of future combination therapies for Alzheimer's disease and tauopathies." Branislav Kovacech, PhD., Chief Operating Officer: "The ATP and PTP platform trials fundamentally change how drugs are developed. Instead of isolated, lengthy, and expensive studies, a dynamic infrastructure is emerging in which the most devastating brain diseases are studied more efficiently - with fewer patients on placebo and faster pathways for promising therapies. This is a major advantage for both patients and investors." Michal Fresser, Chief Executive Officer: "The fact that NIH, UCSF, Harvard, and leading U.S. centers have chosen AADvac1 as the first tau therapy in the Alzheimer's Tau Platform and as one of the first therapies in the PSP Platform is not only a scientific milestone but also a strategic validation of our approach. It is clear evidence that technology developed by our innovators has the potential to become part of future treatment standards for Alzheimer's disease and PSP." Media Contact Email: media@axon-neuroscience.eu SOURCE: Axon Neuroscience, a.s. View the original press release on ACCESS Newswire

编者按 痴呆及认知障碍仍是全球公共卫生领域面临的严峻挑战。2025年，国际痴呆及认知障碍领域在发病机制、预防、诊断和治疗方面均取得了一系列重要突破。单细胞测序等多组学技术的深入应用，为揭示痴呆的发病机制提供了全新视角；生活方式风险因素的持续干预在疾病预防中仍具关键作用；新型生物标志物的开发与临床转化，显著提高了阿尔茨海默病（AD）早期诊断能力。本文将对2025年痴呆及认知障碍领域新紧张做以简单的整理。 一、柳叶刀发布 (AD)专刊文章揭示诊疗现状及未来挑战 《Lancet》重磅发布最新阿尔茨海默病 (AD)专刊发布了系列文章，系统阐述了该领域在诊断、治疗与预防策略上的重大突破。其中在诊疗现状及挑战方面指出：2024 年全球共有 182 项 AD 随机临床试验，其中 30% 测试疾病修饰生物制剂，43% 测试疾病修饰小分子，14% 测试认知增强剂，11% 测试神经精神药物。仅 33% 的试验药物以 β- 淀粉样蛋白和 tau 蛋白为靶点，其余药物覆盖肠道 - 脑轴、血管系统、表观遗传学、昼夜节律、生长因子与激素、APOE 状态、脂质代谢、神经发生、氧化应激、蛋白质代谢、生物能量学、突触可塑性、神经递质受体、炎症与免疫等多元机制。目前已有试验探索抗 β 淀粉样蛋白与抗 tau 单克隆抗体联合治疗（NCT05269394），这种靶点多样性反映了 AD 研究从淀粉样蛋白级联假说的决定论观点，向兼顾共病与机体韧性的复杂病理生理学模型转变的趋势。 尽管临床试验数量众多，但 AD 治疗仍面临显著未满足需求，现有药物难以实现疾病逆转或显著延缓进展，治疗效果有限且个体差异较大，亟需更精准的治疗靶点与更有效的干预策略。 二、认知障碍发病机制领域新进展 Aβ病理 在Aβ病理的研究方面，加州大学团队发表在Cell上的研究首次发现了一种可作为转录因子的代谢酶——磷酸甘油酸脱氢酶，通过激活星形胶质细胞中促炎因子的转录，促进神经炎症和Aβ病理的形成。另外，Cai等人首次运用邻近标记亚细胞蛋白质组学技术，确立了髓鞘-轴突界面是Aβ聚集与信号失调的关键部位。  tau病理 关于tau病理，伦敦大学研究人员首次揭示了特定的可溶性高分子量tau蛋白（而非tau神经纤维缠结）可通过抑制海马神经元电活动直接破坏记忆环路。瑞典哥德堡大学的研究团队首次在AD患者脑组织中鉴定出由氨基酸258~368构成的可溶性tau聚集核心及其关键磷酸化位点，揭示了可溶性tau聚集物在神经纤维缠结形成前即直接驱动神经元功能障碍。 同时， Watamura等人也发现过度磷酸化tau蛋白在形成具有传播活性的聚集物之前，便可直接导致神经元突触丢失和小鼠认知缺陷。此外一篇发表在Nature的研究首次揭示锂稳态破坏是AD早期致病事件，锂缺乏可驱动Aβ沉积与tau病理，为理解AD发病机制提供了新思路。 三、诊断标志物新进展 血浆生物标志物p-tau181与p-tau217水平能够测量β淀粉样蛋白引发的可溶性Tau蛋白磷酸化变化。最新研究表明，衰老过程中常见的溶酶体酸度丧失现象，会导致此类磷酸化Tau生物标志物的释放。Tau蛋白的磷酸化会以pH值依赖的方式阻碍蛋白酶对其进行切割，这为阿尔茨海默病中磷酸化Tau生物标志物的积累提供了新的分子机制解释。 新近研发的血浆生物标志物“内源性切割MTBR-tau243（eMTBR-tau243）”展现出对阿尔茨海默病相关Tau蛋白缠结病理特征的特异性识别能力。与其他磷酸化Tau标志物不同，血浆eMTBR-tau243水平与阿尔茨海默病临床严重程度及Tau蛋白PET分期呈强相关性。由于其临床检测便捷且成本较低，血浆eMTBR-tau243有望成为对疾病分期、临床试验受试者筛选或研究终点评估具有重要价值的工具，为Tau蛋白PET显像或脑脊液MTBR-tau243检测提供了替代方案。 同时，阿尔茨海默病协会在2025年阿尔茨海默病国际大会（AAIC）上发布了首份基于循证医学的临床实践指南（CPG），该指南针对血液生物标志物（BBM）检测的应用提出专业建议，标志着专科诊疗领域阿尔茨海默病诊断与管理方式的重大革新。 在PET分子标志物方面，tau蛋白PET成像有望实现AD更早期、更准确地诊断。一项发表于JAMA的纵向队列研究发现, 在认知功能正常的参与者中，92% tau PET阳性受试者的Aβ PET也是阳性，且Aβ PET与tau PET双阳性者与单阴性或双阴性者相比，在5年内进展为轻度认知障碍或痴呆的风险显著增加。 郁金泰教授团队研究证实，新型第二代示踪剂18F-Florzolotau PET在诊断不同类型tau蛋白病方面具有优异性能，该技术使得约19.3%患者的诊断被修正，总体诊断置信度从68.6%显著提升至81.3%，并促使22.2%患者的临床管理策略发生改变。 四、治疗领域新进展 在痴呆症治疗领域，2025年是至关重要的一年，抗淀粉样蛋白治疗现已融入全球临床实践。过去一年的证据表明，抗淀粉样蛋白治疗在真实世界临床实践中依然有效。这一验证结果尤为重要，因为临床试验之外的临床实践中，治疗对象往往是年龄更高、身体更虚弱、认知衰退更严重的患者。一项大型行为神经病学学术性实践研究结果表明，阿尔茨海默病新型抗体药物仑卡奈单抗（lecanemab）治疗后出现淀粉样蛋白相关影像学异常（amyloid-related imaging abnormalities, ARIA）的发生率与临床症状严重程度相关，强调了早期治疗的重要性。 在抗淀粉样蛋白治疗不断发展的同时，靶向清除Tau蛋白的新型分子策略也相继涌现，包括反义寡核苷酸、亚型特异性Tau抗体以及小干扰RNA等药物。当前的临床试验也在关注将Tau蛋白水平降低作为治疗靶点的疗效，并与抗淀粉样蛋白药物联合疗法的疗效进行对比。阿尔茨海默病Tau蛋白平台试验（注册号NCT06957418和NCT07167966）目前正在针对处于阿尔茨海默病的临床前晚期或前驱期早期的50-80岁成年患者展开研究，评估AADvac1作为单药治疗或与抗淀粉样蛋白单克隆抗体联合用药的疗效。 五、碱酯酶抑制剂在遗忘型轻度认知障碍阶段的真实世界研究 首都医科大学宣武医院贾建平教授团队开展的关于胆碱酯酶抑制剂在轻度认知障碍阶段疗效的真实世界纵向研究，在《Alzheimer’s & Dementia》以 “The impact of cholinesterase inhibitors on cognitive trajectories in mild cognitive impairment patients based on amyloid beta status” 正式发表。 这项纳入558例遗忘型轻度认知障碍（amenstic mild cognitive impairment）患者长达10年随访数据的队列研究，首次在考虑Aβ病理状态的基础上，系统揭示了胆碱酯酶抑制剂（cholinesterase inhibitors）未能延缓遗忘型轻度认知障碍向阿尔茨海默病痴呆（Alzheimer’s dementia）的转化进程或减缓认知衰退速度，应重新审视ChEI在aMCI阶段的临床应用。 六、互联网使用对中国老年人认知障碍的影响及社会参与的调节作用！ 2025年12月在《BMC Geriatrics》杂志上发表了题为《The impact of Internet usage on cognitive impairment among Chinese older people: a social participation perspective》的文章。该研究探讨了互联网使用模式与中国老年人认知功能之间的关联。分析了8349名参与2020年中国健康与退休纵向研究（CHARLS）的受访者数据，结果显示互联网使用与认知得分显著相关。尤其是观看新闻和玩游戏对认知功能有积极影响，分别提高了认知得分。通过台式电脑和手机上网也与更高的认知得分相关。 研究发现社会参与在互联网使用与认知功能之间起到部分调节作用，特定人群如城市居民、女性和71至80岁者效果更显著。结论指出，改善互联网接入和使用，并增强社会参与，有助于促进老年人的认知健康。 七、额颞痴呆与阿尔茨海默病和帕金森病中的共享及疾病特异性通路 神经退行性疾病（NDs），如阿尔茨海默病（AD）、帕金森病（PD）和额颞痴呆（FTD），表现出不同但重叠的病理机制。2025年发表在nature medicine的一项研究，其利用全球神经退行性退行性蛋白质组学联盟的大规模血浆蛋白质组学数据，我们分析了10,527个血浆样本（1,936个AD，525个PD，163个FTD，1,638个痴呆，6,265个对照组），以识别疾病特异性及神经发育组间共享的蛋白。我们鉴定出5,187种与阿尔茨海默病显著相关的蛋白质，3,748种与帕金森病相关，2,380种与FTD相关，这些蛋白显示出共同和发散的蛋白质组特征，这些特征通过多种分析方法和正交验证得到证实。PD和FTD重叠度最高（r 2 = 0.44），AD和PD重叠最少（r 2 = 0.04）。 该研究首次系统性研究神经退行性疾病的血浆蛋白质组学，其构建的血液检测模型可使FTD诊断准确率达88%。相较于昂贵而不可及的PET影像检查或创伤性较大望而却步的腰椎穿刺，这一突破为早期筛查提供了安全、经济的可行性方案，助力FTD精准诊断，并为靶向治疗研发奠定分子基础。 八、路易体痴呆的遗传学与病理学新发现 2025年《柳叶刀神经病学》重磅推出路易体痴呆专刊，系统回顾了该领域十年的突破性进展。这期专刊不仅总结了过往成果，更指明了未来方向。编辑在开篇社论中深情回顾了三十年的科研征程，其中在疾病症状的精细化管理及疾病修饰疗法提出相关观点。 症状的精细化管理：目前，治疗依赖于多管齐下的综合策略。胆碱酯酶抑制剂是改善认知和神经精神症状的基石；左旋多巴可缓解运动症状；此外还需管理睡眠、情绪和自主神经功能障碍。专家共识强调，应优先使用非药物干预，并谨慎使用可能加重病情的药物。 疾病修饰疗法的曙光：研究的重心正转向能从根本上延缓或阻止疾病进展的疗法。多项临床试验正在测试：靶向α-突触核蛋白：通过抗体或疫苗清除有毒蛋白。靶向阿尔茨海默共病理：直接使用获批的阿尔茨海默病药物（如Lecanemab）来治疗具有相应生物标志物的患者亚组。针对新兴靶点：如抑制神经炎症、增强溶酶体功能甚至利用降糖药等，多种新途径正在被探索。 九、动脉粥样硬化诱导血管性认知障碍的新机制 过去几十年的研究表明，动脉粥样硬化与VCI的发展有关，二者“共享”年龄、糖尿病和高血压等多种风险因素。动脉粥样硬化是导致血管狭窄的主要原因，通常被认为能够通过减少脑血流量促进缺血性白质损伤和VCI。不过，由于干扰因素太多，这其中具体的机制还不是很清楚。 2025年《细胞·代谢》杂志上，由华中科技大学同济医学院附属同济医院秦川教授、田代实教授和王伟教授领导的研究团队发表相关研究发现：动脉粥样硬化斑块中，由巨噬细胞衍生的泡沫细胞产生的外泌体通过miR-101-3p-Nrf2-Slc2a1轴将线粒体功能障碍和代谢缺陷传递给小胶质细胞，促进了缺血性脱髓鞘。抗miR-101-3p或激活Nrf2的治疗可以改善VCI。这项研究不仅为VCI的机制和治疗提供了新的见解，还揭示了外周巨噬细胞和大脑小胶质细胞的联系。 十、遗传性额颞叶变性诊断突破，大规模脑脊液蛋白谱揭秘核心机制 荷兰神经内科和阿尔茨海默中心联合多国团队在神经科学顶刊《Brain》上发表了一项开创性研究，通过大规模脑脊液（CSF）蛋白质组学分析，首次系统揭示了遗传性额颞叶变性（FTLD）不同遗传亚型的特异性分子特征，并开发出诊断准确率高达96%的蛋白组合工具。这一成果不仅为临床诊断提供了新思路，更深入解析了疾病背后的病理机制。 该研究不仅为FTLD病理机制的理解提供了深入见解，更提供了里程碑式突破的诊断工具。该研究核心价值不仅在于发现了亚型特异性蛋白特征和高准确性诊断panel，也验证了Olink PEA技术在神经退行性疾病体液标志物研究中的优势，为后续相关研究提供了可借鉴的技术方案和研究框架。开发的两个诊断Panel在独立队列中表现出色，有望应用于FTLD的临床诊断、鉴别诊断及临床试验入组，最终改善患者的诊疗结局。 编辑 | 暖暖 排版 | 暖暖 审核 | 三顺 期待你的“分享”、“点赞”、“在看”