The Salk Institute for Biological Studies

CoLab session with PrognomiQ and Salk Institute plus multiple presentations of new data offer firsthand look at multi-omic breakthroughs powered by Seer’s Proteograph™ Product SuiteREDWOOD CITY, Calif., Oct. 31, 2024 (GLOBE NEWSWIRE) -- Seer, Inc. (Nasdaq: SEER), a leading life sciences company commercializing a disruptive new platform for proteomics, will showcase the Proteograph Product Suite’s unique ability to deliver deep proteomic insights that complement and strengthen genomic and other “omic” research at the American Society of Human Genetics (ASHG) 2024 Annual Meeting in Denver, Colo., from Nov. 5-9. Seer will present a CoLab session exploring research breakthroughs from PrognomiQ and Salk Institute, as well as several presentations in the scientific sessions, all enabled by the industry-leading capabilities of Seer’s Proteograph Product Suite. Covering prominent disease areas like lung cancer and Alzheimer’s Disease, as well as conditions scientists are only starting to understand, such as Relative Energy Deficiency in Sport (REDs), these sessions will explore how Seer is linking powerful proteomic capabilities at previously unattainable depth, scale, and speed, with genomic data to produce a compelling and growing body of advanced research. “Advancements in genomic research in recent decades have significantly enhanced our understanding of biology and human health,” said Asim Siddiqui, PhD, Senior Vice President, Research and Tech Development at Seer. “With the Proteograph Product Suite, we are now able to combine deep proteomics at scale with deep genomics at scale and push the boundaries of biological insight, opening up new frontiers in scientific discovery. At Seer, we are excited to see our Proteograph Product Suite at the forefront of so many of these multi-omic breakthroughs, and we believe we are just scratching the surface of what is possible.” Seer CoLab Session at the ASHG 2024 Annual Meeting: The Power of Deep Proteomics: Driving the Next Generation of Genomic Research Unleashing the Power of Multi-omics: A Breakthrough in the Early Detection of Lung Cancer Philip Ma, PhDCEO & Founder, PrognomiQ, Inc. Lung cancer remains a leading cause of death globally, driven in large part by its detection only in late and advanced stages of cancer. Thus, early detection is crucial for improved outcomes, but current screening methods, such as low-dose CT scans, face limitations in adherence and sensitivity. Philip Ma and colleagues are exploring a multi-omics biomarker test that leverages the power of proteomics, transcriptomics, and metabolomics to detect early-stage lung cancer. Their study, the MOSAIC study, employed a deep and untargeted exploration of the plasma proteome, coupled with transcriptomic and metabolomic data. This comprehensive approach enabled them to identify a panel of biomarkers that can accurately discriminate between lung cancer patients and controls, even in the early stages of the disease. By combining multiple molecular data types, their multi-omics classifier offers a more sensitive and specific approach to lung cancer detection. This classifier demonstrated exceptional sensitivity for all-stage, stage I, and stage II-IV lung cancer, outperforming existing published studies. This breakthrough enables the development of a blood-based lung cancer detection test, with the potential to significantly improve early diagnosis, leading to better treatment outcomes and reducing mortality rates. “To truly make a difference for the millions of patients each year who are diagnosed with lung cancer, we must find ways to detect the disease sooner when the chances of treatment and survival are more favorable,” said Philip Ma, CEO and Founder of PrognomiQ. “The work we’re doing using Seer’s Proteograph platform is enabling us to transform early lung cancer detection, giving us real hope that more lives can be saved.” Mouse Model of Relative Energy Deficiency in SportLaura van Rosmalen, PhDSatchidananda Panda Lab, Salk Institute for Biological Studies Relative Energy Deficiency in Sport (REDs) is associated with insufficient energy intake and excessive energy expenditure. This state of low energy availability can result in systemic neuroendocrine and metabolic abnormalities affecting health and performance. Studies on mice have shown that the effects of REDs can be wide-ranging, including significant shrinkage of vital organs like the kidney and reproductive organs, deterioration of bone quality, and negative psychological consequences. Despite the high prevalence (affecting 40 percent of athletes), little is known about how REDs impacts the body at the molecular level. This has made it difficult to understand REDs, its diagnosis and treatment, and highlights the importance of an animal model of REDs. Deep proteomic insights are helping to reveal protein signatures of REDs, with important implications for metabolic health and athletic performance. “A multi-omics approach, including unbiased proteomics, is arguably even more important for a condition like REDs for which little is known about its diagnosis, effects, or potential treatments,” said Satchidananda Panda, PhD, Director, Wu-Tsai Human Performance Alliance at Salk Institute. “Seer’s technology allows our team to understand REDs on a cellular and molecular level, which in turn could lead to diagnostic tests and therapies to halt, reverse, or prevent it entirely.” Highlights From Seer and Collaborators Presenting at the ASHG 2024 Annual Meeting: Seer Title: A Genome-wide Association Study of Mass Spectrometry Proteomics Using the Seer Proteograph PlatformPresenting Author: Serafim Batzoglou, PhDDate & Time: Nov. 6, 2:30 - 4:30 p.m. Seer Title: Understanding the Impact of Genetic Variants on Alzheimer’s Disease With Mass Spectrometry ProteogenomicsPresenting Author: Harendra Guturu, PhDDate & Time: Nov. 7, 2:30 - 4:30 p.m. New York University Title: Multi-omic Profiling in a 61-day Pig Kidney to Human Decedent Xenotransplant Reveals a Concerted Acute Rejection Immune ResponsePresenting Author: Brendan Keating, PhDDate & Time: Nov. 6, 11:15 a.m. About Seer: Seer is a life sciences company developing transformative products that open a new gateway to the proteome. Seer’s Proteograph Product Suite is an integrated solution that includes proprietary engineered nanoparticles, consumables, automation instrumentation and software to perform deep, unbiased proteomic analysis at scale in a matter of hours. Seer designed the Proteograph workflow to be efficient and easy to use, leveraging widely adopted laboratory instrumentation to provide a decentralized solution that can be incorporated by nearly any lab. Seer’s Proteograph Product Suite is for research use only and is not intended for diagnostic procedures. For more information, please visit www.seer.bio. For more information, please visit booth #335 or contact us at pr@seer.bio. Media Contact: Patrick Schmidt pr@seer.bio Investor Contact: Carrie Mendivil investor@seer.bio

• 波士顿的经验，或许可以成为香港的借鉴； • 波士顿和加州的成熟主要得益于强大的创新、创业与投资生态系统，香港正在构建这样的生态系统； • 香港设立的药械审批机构CMPR如何运作及应达成何种目标，成为香港热议的焦点。 • 香港计划在河套深港科技创新合作区建立“大湾区国际临床试验所”，提供一站式临床试验支持。 美国旧金山和圣地亚哥在上世纪60~70年代，凭借斯坦福大学、UC伯克利大学、Salk、Scripps等高校和科研机构，和基因泰克、安进、吉列德等公司及创新的投融资氛围，在生物技术领域迅速崛起。而彼时，大波士顿都市区的生物科技转化已落后了20年。但从2007年起，马萨诸塞州通过减免税收、吸引人才政策，10年内在生物技术领域投资超15亿美元，创造了近千家生物技术公司和超10万个工作机会，平均年薪超20万美元，并获得了NIH大约1/10的资金支持。2022年，该地区获风险投资51亿美元。由此，大波士顿成功逆袭加州。 波士顿的经验，或许可以成为香港的借鉴。事实上，香港的生物医药需要明确定位。是自主创新，还是以CRO/CDMO、平台技术检测等服务型工作，抑或利用金融优势成为孵化融资中心？作为生物医药“超级连接者”（Supper Connector)和“超级价值赋能者”(Supper Value Adder)的香港，正面临抉择。 香港拥有什么优势？ 在BIOHK2024一场“香港：全球生物医药超级价值赋能者”的讨论上，业内资深专家冯博士用上述波士顿的故事勉励香港。他说：“尽管香港的生物医药生态系统和科学氛围可能暂时落后于长三角，但随着香港各项鼓励政策密集出台、大量资金的扶持以及全球顶尖人才的汇聚，香港完全有可能复制大波士顿区的模式，像后者追赶加州生物科技领域那样，后来者居上。” 冯博士是土生土长的香港人，他18岁离开香港赴美求学，拥有丰富的中美监管、产业和投资经验。 艾昆纬大中华区商业服务总经理邵文斌介绍了北京、长三角生物医药园区在资金与人才方面的大力扶持，吸引了大量的海归回来创办企业，在这一点上，值得香港借鉴。他指出，一个区域要成为生物技术中心，需要具备城市建设、政策扶持、研发资源、创新体系、融资能力及企业集聚六大要素。 “历史上，香港以金融和专业服务著称，但如今，重点正转向生物科技和人工智能的创新。”香港生物科技协会副主席，银标资本联合创始人梁传昕博士代表香港在这场讨论上回应说，香港特区政府已认识到，有必要为香港在生物技术领域的发展制定清晰的路线图，并出台相关政策以促进增长，吸引顶尖人才和投资。 香港拥有5所全球70强大学，这一数量超过伦敦、东京和纽约，还有全球排名前40的医学中心与联合实验室，建立了与国际接轨的科学体系和人才梯队。此外，梁传昕说，港交所是过去十年IPO累计募集资金领跑全球的交易所，对推动香港生物科技发挥了重要作用。自2018年以来，得益于监管变革，生物技术领域的IPO数量激增。“尽管IPO数量和估值会随市场周期而波动，但整体趋势仍然积极，使香港在这一领域占据重要地位。” 波士顿和旧金山的成熟主要得益于强大的创新、创业与投资生态系统，而香港正在构建这样的生态系统。 香港拥有顶尖医院和临床试验中心，作为全球预期寿命最长地区，是医学研究的理想地，吸引专注临床研究的生物技术公司。就在不久前，香港卫生局局长卢宠茂教授倡议创建第三所香港医学院，旨在解决香港面临的医生数量不足和医疗资源分配不均等问题。目前这一动议得到了香港各界广泛的认可和支持。 卢宠茂也出席了此次大会，他专门谈到香港应该充分利用高质量和高效的医疗保健资源和系统、尖端的医学、临床研究人才以及研究中心在内的自身优势。 “我们旨在与国家政策保持一致，进一步推动香港的医学水平和临床试验能力。凭借超过8600万人口的基础，香港正在创建一个协同的生态系统以促进医疗保健和临床研究的创新。”卢宠茂说。 卢宠茂教授 据了解，香港计划在河套深港科技创新合作区建立“大湾区国际临床试验所”，为公私营医疗机构提供一站式临床试验支持，以促进临床试验，推动新药研发。 在产业园区规模上，香港虽然“无法与内地相提并论”，但梁传昕认为，香港园区的服务和建设能更国际化，同时，香港拥有众多杰出的教授，他们或许不适合担任公司CEO，但却能胜任企业科学顾问的角色。“这些企业可以将主体设在内地、海外，而在香港保留科学团队及部分研发功能，类似于波士顿的模式。香港无需凡事亲力亲为。” 张曼莉女士 香港科技局副局长张曼莉女士在这次大会上透露，香港政府正致力于构建一套完善的支持创新的基础设施，如去年底成立的系列毒理学平台，提供高临床毒理学化验服务以及各大临床研究中心等，她认为香港应当为创新研发提供更多的赋能平台。 香港发展自主创新靠什么？ 不过，香港仍有待完善之处。刘彦燊是一位在深圳创业的香港人。从2021年开始，出任湃诺瓦医疗总裁，一家专注于神经外科的医疗器械公司。他注意到香港近年对高端人才采取了有利政策以吸引人才。然而，虽有吸引高端人才的政策，但香港仍然面临严峻挑战。尽管这里尝试吸引高端人才，从创业的角度来看是不足够的。他认为，除吸引创始人外，还需提供进一步的便利政策、支持和资源，助其在港组建团队、发展业务。 刘彦燊认为，香港在吸引特定领域中端人才方面仍有不足，研发、制造、质量体系等团队的建立，世界100强高校的毕业生不一定能够胜任，需要的是在该些细分领域拥有5-15年以上“动手”经验的专业人才。一些在药物和器械领域工作的朋友最终选择去上海、北京或留在美国，而不是香港，一个重要原因是他们在香港难以组建一个能够协助创始人从0到1把产品做出来的团队。 因此，他个人选择周一到周五在深圳生活，部分原因也是深圳在创业和人才聚集方面有更好的环境。 “香港在吸引和留住人才方面仍有待加强。不过，我依然对未来港内地及国际人才交流持乐观态度，相信会有更多优秀人才来港，同时港人也能赴内地，共同促进人才交流与多元化发展。” 刘彦燊说。 滬港中科公共事务总监马骏一是内地人，3年前转战到香港工作，见证了新一届特区政府鼓励发展创科的巨大决心以及医药创新的变化，给他印象最深刻的是，去年特首施政报告中提及的香港筹备成立CMPR（即俗称的“港版FDA”），香港的药品监管正在从“二级审批”积极转向“一级审批”。三年前行业讨论的是港版FDA要不要做，现在大家讨论最多的是CMPR要怎么做，要做成什么样子。 在实际工作中，他发现困扰香港业界多年的难题一直未解决：香港临床研究机构申请NMPA资质认证缺少法规路径。例如，在GCP方面，尽管香港有4家医院，部分科室已获得GCP认证，但对新科室或新医院而言，想要获得认证或备案却面临无法可依，无章可循的困境。而在GLP和GMP领域，至今没有一家香港机构获得NMPA的资质认证。 “香港没有独立的药品审批机构和审评审批体系，是既往本地创新遇到的独特挑战。”马骏一说，他坚定支持香港要尽快建立自己的CMPR，并且在制度顶层设计时就要考虑到与全球监管体系（ICH,PIC/S等）的接轨。帮助中国医药创新企业走向世界，不仅是发达国家，如何更便捷地走入一带一路沿线国家也应该是CMPR必须要考虑的。 拓展阅读  港版FDA如何以观察员加入ICH？ 前FDA资深审评员、CDE首席科学家、荣昌生物首席战略官何如意博士也参加了BIOHK2024。他告诉研发客，CMPR体系在香港的建立有着充分性和必要性，这是因为由于香港的疾病分布、用药习惯及药品种类与美国及内地都存在差异，香港独立的监管机构未来以自身需求为主，对内地符合国际标准的产品如通过一致性评价的仿制药即可申请香港上市。中国内地产品可通过香港走向东南亚，走向世界。“CMPR体系与NMPA之间存在多方合作潜力，包括加强沟通交流、开展核查及稽查工作。”他建议说。 何如意博士 “香港CMPR的官方语言之一是英语，这导致在申报流程中的文件撰写、提交及沟通交流上，香港与内地形成了不同体系。此外，香港的工作方式、流程也与内地不同。未来CMPR将解决香港自身生物医药公司申报过程中的问题。”前FDA官员胡育志博士对此评价道。 香港生物医药未来的定位将很大程度受香港CMPR的影响，邵文斌如是认为。他从几方面提出建议：应从监管科学着手，制定政策以激励先进疗法研发，如细胞与基因治疗技术指导原则；针对香港及东南亚地区尚未得到充分疾病谱，鼓励内地与香港的合作，或支持香港本土生物技术公司进行相关研发；此外，应充分利用 “港澳药械通”等大湾区机制，探索药品与医疗器械相结合的新型治疗手段，发挥香港在医疗器械与诊断试剂领域的专长，细分化发展，找到香港独特的突破点。 冯博士认为，香港凭借在全球排名前列的高校，短期内依然以基础科研为主，如果要做自主创新，眼下不能一步到位，需要以建立转化为主的平台，但长期而言香港具备拥有像大波士顿那样的潜力，吸引众多生物技术公司开展自主创新。就在今年初，上海医药联手香港科技园启动创新孵化器。他认为，这是香港科研转化一个良好的开始。 拓展阅读  1:1政府补贴，香港孵化上海转化的新型探路 香港生物医药创新协会会长卢毓琳认为，香港在医疗诊断与器械领域已经奠定了坚实的基础。短期内，这些领域可以成为发展的重点之一，因为它们能更快地带来收益。从长远来看，发展应依据临床和市场需求。在这方面，投资人以其敏锐的市场洞察力，可以作为重要的风向标。 刘彦燊认为，若香港定位于提供服务，其根本依然需依托于创新。他指出，“如果香港缺乏创新型企业，CXO公司又何从获取订单呢？” 从左至右：邵文斌、冯博士、研发客主编毛冬蕾、梁传昕、刘彦燊、马骏一 除了去年参会的国内企业，研发客还留意到一些新来者。 拓展阅读  香港能否成为回国创业第一站? 君圣泰医药的创始人和董事会主席刘利平博士今年第一次参加BIOHK2024大会。该公司已于2023年10月成功入驻香港科技园，并以此作为全球运营核心，推进临床研究及创新药物发现模式的引入。君圣泰立足源头创新赢得了香港政府的认可，被授予“重点企业伙伴”称号。刘利平说，香港政府积极吸引高潜力企业，尤其是在生命健康科技领域，其独特的国际地位和积极的产业扶持政策是君圣泰选择入驻的关键因素。 专注于小核酸药物的海昶生物CEO赵孝斌告诉研发客，其公司去年底在香港科学园设立办事处。赵孝斌说，落户香港科学园的公司，政府给予1:1的补贴且不占股权，同时招聘大量全球化人才，加之香港的投资人资源和海外拓展网络的优势，使得海昶生物决定落户香港。 杭州中赢生物的副总裁兼首席科学家陈霖博士首次受邀参会，他介绍了公司在免疫细胞，特别是NK细胞制备工艺上的成就。中赢生物专注于免疫细胞的存储与应用，集研发、生产、营销于一体。他说，香港丰富的临床资源和在免疫细胞疗法IIT方面的经验及香港数据在东南亚的认可度，使得香港成为连接内地与东南亚市场的桥梁。中赢生物未来有计划在香港开展临床试验并设立项目。 于常海博士 香港生物科技协会主席于常海博士说，香港有中国政府官方支持、更靠近生物技术的中心，香港交易所18A章允许无收入的生物技术公司上市，作为一个生物医药的“超级联系人和赋能者”，香港是帮助内地生物科技走向世界、世界生物科技到内地发展的平台，香港正在推动生物技术的黄金时代，而BIOHK2024是通往全球生物技术市场的门户。 BIOHK 2024精彩瞬间 中国人民政治协商会议全国委员会副主席梁振英发表了题为“三中全会《决定》在科学领域的进一步全面深化改革——香港扮演什么作用”的主旨演讲。他特别强调，香港亦需将进一步全面深化改革视为己任，特别是在科学领域探索和实践这一改革路径的重要性，以展现香港在国家整体发展战略中的独特贡献与价值。 中国科学院院士、中国微生物学会理事长、中国科学院微生物研究所研究员高福教授发表了题为“中国生物技术产业展望：2024及未来”的报告，剖析了当前中国生物医药领域从国家战略规划到具体行业发展现状，展望了这一领域中国的未来趋势与潜力。 于常海和香港创新科技及工业局局长孙东为香港中文大学副院⻓卢煜明教授（右二）颁奖。 出席BIOHK 2024香港生物科技行业的名流。 编辑 | 姚嘉 yao.jia@PharmaDJ.com  总第2200期 访问研发客网站，深度报道和每日新闻抢鲜看 www.PharmaDJ.com

Alzheimer's disease (AD), a disease that severely impairs the brain's thinking, cognitive and memory functions, affects more than 30 million people worldwide. When discussing potential triggers for the disease, it is not difficult to think of the tangles caused by beta-amyloid protein (Aβ) and abnormal tau proteins. These two pathological factors not only cause direct damage to nerve tissue and cells, but also induce inflammation and destroy nerve function. Further evidence suggests that the phenomenon associated with Aβ and tau tangles is A disorder of glucose metabolism in multiple regions of the brain. In the case of astrocytes, the cell produces lactic acid through metabolism to support mitochondrial activity and synaptic activity, which is essential for the healthy function of other neurons. However, the brain glucose metabolism of AD patients is generally decreased, and the supporting role of astrocytes is greatly weakened, further leading to cognitive and memory dysfunction. In the latest issue of the journal Science, scientists from the Salk Institute for Biological Studies and Penn State University collaborated to discover that an enzyme called IDO1 is able to break down tryptophan into kynurenine. When IDO1 is overactive and activates the kynurenine pathway, it reduces glucose metabolism in astrocytes and reduces lactate production required by neurons, driving the progression of AD symptoms. In contrast, the use of IDO1 inhibitors in AD mice successfully restored astrocyte function and improved mouse memory. In the field of oncology, IDO1 has become a hot molecule of research interest, and clinical trials have been conducted to test the anticancer effects of IDO1 inhibitors. For example, a Phase 1 clinical trial found that the IDO1 inhibitor PF-*** (PF068) reduced kynuridine levels in patients with glioblastoma, and nearly half of patients treated with PF068 had their disease under control. Work in the field of oncology has saved valuable time for drug screening for new studies. The research team tried using the IDO1 inhibitor PF068 in a mouse model of AD, and the results showed that glucose metabolism in the hippocampus of the mice returned to normal levels, astrocyte function was restored, and memory function in AD mice was significantly improved, suggesting that this potential cancer treatment drug may also play a role in AD treatment. In the experiment, the authors first constructed an AD mouse model with pathological characteristics of Aβ and tau proteins, and analyzed astrocytes in brain samples. The results showed that both pathological features caused a significant increase in the mRNA level of IDO1 in cells and increased kynurenine production. They then injected PF068 into mice, where not only was astrocyte IDO1 decreased, but genes in the downstream pathway of kynuridine were also inhibited. On the contrary, the expression of glycolytic-related genes increased again. The authors found that with the addition of PF068, glycolytic intermediates, lactic acid and mitochondrial oxidative phosphorylation processes were restored. In addition to astrocytes being affected, studies have shown that increased IDO1 also disrupts glucose metabolism in the hippocampus, impairs synaptic elasticity in this brain region, and causes impairment in memory function. In memory tasks, mice with AD models without any processing tended to perform worse. However, after treatment with IDO1 inhibitors, the performance of AD mice was significantly improved, and their spatial memory and long-term memory were restored. Dr. Paras Minhas, co-first author of the study, noted that current treatment strategies targeting Aβ or tau protein tangles can be effective in slowing disease progression, but what the new study saw in mice shows that targeting brain metabolism holds promise for further reversing disease progression. These findings support the idea that lactic acid produced by astrocytes plays an important role in supporting neuronal function. Professor Katrin Andreasson, corresponding author of the study, said that the IDO1 inhibitor improved AD symptoms in mice, both for Aβ and tau protein-associated AD mouse models, suggesting that it could work in A wide range of AD individuals. In the future, they plan to test the effects of IDO1 inhibitors in clinical trials in AD patients to see if the drug can also help reduce cognitive and memory dysfunction in humans. Alzheimer's disease (AD), a disease that severely impairs the brain's thinking, cognitive and memory functions, affects more than 30 million people worldwide. When discussing potential triggers for the disease, it is not difficult to think of the tangles caused by beta-amyloid protein (Aβ) and abnormal tau proteins. These two pathological factors not only cause direct damage to nerve tissue and cells, but also induce inflammation and destroy nerve function. Further evidence suggests that the phenomenon associated with Aβ and tau tangles is A disorder of glucose metabolism in multiple regions of the brain. In the case of astrocytes, the cell produces lactic acid through metabolism to support mitochondrial activity and synaptic activity, which is essential for the healthy function of other neurons. However, the brain glucose metabolism of AD patients is generally decreased, and the supporting role of astrocytes is greatly weakened, further leading to cognitive and memory dysfunction. In the latest issue of the journal Science, scientists from the Salk Institute for Biological Studies and Penn State University collaborated to discover that an enzyme called IDO1 is able to break down tryptophan into kynurenine. When IDO1 is overactive and activates the kynurenine pathway, it reduces glucose metabolism in astrocytes and reduces lactate production required by neurons, driving the progression of AD symptoms. In contrast, the use of IDO1 inhibitors in AD mice successfully restored astrocyte function and improved mouse memory. In the field of oncology, IDO1 has become a hot molecule of research interest, and clinical trials have been conducted to test the anticancer effects of IDO1 inhibitors. For example, a Phase 1 clinical trial found that the IDO1 inhibitor PF-*** (PF068) reduced kynuridine levels in patients with glioblastoma, and nearly half of patients treated with PF068 had their disease under control. Work in the field of oncology has saved valuable time for drug screening for new studies. The research team tried using the IDO1 inhibitor PF068 in a mouse model of AD, and the results showed that glucose metabolism in the hippocampus of the mice returned to normal levels, astrocyte function was restored, and memory function in AD mice was significantly improved, suggesting that this potential cancer treatment drug may also play a role in AD treatment. In the experiment, the authors first constructed an AD mouse model with pathological characteristics of Aβ and tau proteins, and analyzed astrocytes in brain samples. The results showed that both pathological features caused a significant increase in the mRNA level of IDO1 in cells and increased kynurenine production. They then injected PF068 into mice, where not only was astrocyte IDO1 decreased, but genes in the downstream pathway of kynuridine were also inhibited. On the contrary, the expression of glycolytic-related genes increased again. The authors found that with the addition of PF068, glycolytic intermediates, lactic acid and mitochondrial oxidative phosphorylation processes were restored. In addition to astrocytes being affected, studies have shown that increased IDO1 also disrupts glucose metabolism in the hippocampus, impairs synaptic elasticity in this brain region, and causes impairment in memory function. In memory tasks, mice with AD models without any processing tended to perform worse. However, after treatment with IDO1 inhibitors, the performance of AD mice was significantly improved, and their spatial memory and long-term memory were restored. Dr. Paras Minhas, co-first author of the study, noted that current treatment strategies targeting Aβ or tau protein tangles can be effective in slowing disease progression, but what the new study saw in mice shows that targeting brain metabolism holds promise for further reversing disease progression. These findings support the idea that lactic acid produced by astrocytes plays an important role in supporting neuronal function. Professor Katrin Andreasson, corresponding author of the study, said that the IDO1 inhibitor improved AD symptoms in mice, both for Aβ and tau protein-associated AD mouse models, suggesting that it could work in A wide range of AD individuals. In the future, they plan to test the effects of IDO1 inhibitors in clinical trials in AD patients to see if the drug can also help reduce cognitive and memory dysfunction in humans.