Precision Medicine for Inflammatory Treatment for Alzheimer's Disease in Down Syndrome

唐氏综合症中阿尔茨海默病炎症治疗的精准医学

• 批准号: 10591821
• 负责人: Michael S Rafii
• 金额: $ 25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10591821
• 关键词: Age; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer’s disease biomarker; Anti-Inflammatory Agents; Antiinflammatory Effect; Clinical Trials; Databases; Disease; Down Syndrome; Immune signaling; Impaired cognition; Individual; Inflammatory; Nerve Degeneration; Neurons; Patients; Persons; Plasma; Proteomics; Research; Sampling; Subgroup; Technology; Testing; Vitamin E; aged; base; biobank; endophenotype; exosome; instrument; nanoparticle; neuropathology; pandemic disease; precision medicine; protein biomarkers; virtual

Supplement Abstract Virtually all Down Syndrome (DS) patients shows neuropathology and cognitive impairment at an accelerated rate as they age, ultimately progressing to Alzheimer’s disease (AD) in older years. Irrespective of so many advances in DS research, we still lack a substantial understanding of AD treatment in the DS patients. In this supplement, we propose to accelerate testing validated protein biomarkers for AD using our established proinflammatory endophenotype analysis in bio-banked samples from the previously completed clinical trial, “Vitamin E in Aged Persons with Down Syndrome.” The study will permit us to understand the inter-relationship between immune signals in DS-AD individuals. In addition, will assist to connect the dots between how prevailing immune signals may impact anti-inflammatory effects on AD biomarkers. The overall objective of our project is to represent a specific subgroup of DS showing a plasma-based proinflammatory endophenotype which would most likely respond to potent anti-inflammatory therapy. We aim to validate inflammatory endophenotype in DS-AD patients and assess changes in AD pathology and neurodegeneration in native plasma and neuronally derived exosomes, both at baseline and longitudinal samples. Utilizing Quanterix Simoa platform HD-X analyzer technology as well as a Nanoparticle Tracking Analyzer Malvern NS-300 instrument, we will be able to accelerate the progress of Aims 1 and 2 to overcome pandemic-related delays as well as maximize high capacity, validated technologies with enhanced capabilities to achieve study aims.

补充摘要 几乎所有唐氏综合症 (DS) 患者都表现出加速的神经病理学和认知障碍 随着年龄的增长，最终会发展为阿尔茨海默病（AD），尽管有这么多人。 尽管 DS 研究取得了进展，但我们对 DS 患者的 AD 治疗仍缺乏实质性了解。 作为补充，我们建议使用我们已建立的方法加速测试经过验证的 AD 蛋白质生物标志物 对先前完成的临床试验的生物库样本进行促炎内表型分析， “患有唐氏综合症的老年人中的维生素 E。”这项研究将使我们了解其中的相互关系。 此外，将有助于将 DS-AD 个体的免疫信号之间的联系联系起来。 普遍的免疫信号可能会影响 AD 生物标志物的抗炎作用。 该项目旨在代表 DS 的一个特定亚组，显示基于血浆的促炎内表型 这很可能对有效的抗炎治疗有反应。我们的目标是验证炎症。 DS-AD 患者的内表型并评估本地 AD 病理学和神经变性的变化 使用 Quanterix 检测血浆和神经来源的外泌体。 Simoa 平台 HD-X 分析仪技术以及纳米粒子跟踪分析仪 Malvern NS-300 工具，我们将能够加快目标 1 和 2 的进展，以克服与大流行相关的延误 以及最大限度地利用高容量、经过验证的技术和增强的能力来实现研究目标。

项目成果

From understanding to action: Exploring molecular connections of Down syndrome to Alzheimer's disease for targeted therapeutic approach.

从理解到行动：探索唐氏综合症与阿尔茨海默病的分子联系，以寻求有针对性的治疗方法。

• 发表时间: 2024
• 作者: Sukreet, Sonal;Rafii, Michael S;Rissman, Robert A
• 通讯作者: Rissman, Robert A

Safety, Tolerability, and Immunogenicity of the ACI-24 Vaccine in Adults With Down Syndrome: A Phase 1b Randomized Clinical Trial.

ACI-24 疫苗在成人唐氏综合症患者中的安全性、耐受性和免疫原性：1b 期随机临床试验。

• 发表时间: 2022-06-01
• 影响因子: 29
• 作者: Rafii, Michael S;Sol, Olivier;Mobley, William C;Delpretti, Saskia;Skotko, Brian G;Burke, Anna D;Sabbagh, Marwan N;Yuan, Shauna H;Rissman, Robert A;Pulsifer, Margaret;Evans, Casey;Evans, A Carol;Beth, Gregory;Fournier, Nicolas;Gray, Julian A
• 通讯作者: Gray, Julian A

Clinical utility of an antibody-free LC-MS method to detect brain amyloid deposition in cognitively unimpaired individuals from the screening visit of the A4 Study.

无抗体 LC-MS 方法在 A4 研究筛选访视中检测认知未受损个体脑淀粉样蛋白沉积的临床应用。

• 发表时间: 2023
• 作者: Allué, José Antonio;Pascual;Sarasa, Leticia;Castillo, Sergio;Sarasa, Manuel;Sáez, María Eugenia;Abdel;Rissman, Robert A;Terencio, Jose
• 通讯作者: Terencio, Jose