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 事实上，所有唐氏综合征（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，最终进展为老年痴呆症（AD）。尽管有这么多 尽管DS研究取得了进展，但我们仍然缺乏对DS患者AD治疗的实质性了解。在这 作为补充，我们建议使用我们已建立的方法加速测试经验证的AD蛋白质生物标志物 来自先前完成的临床试验的生物库样品中的促炎性内表型分析， “维生素E在唐氏综合症老年人中的作用。这项研究将使我们了解相互关系 在DS-AD个体的免疫信号之间。此外，将协助连接点之间如何 流行的免疫信号可能影响对AD生物标志物的抗炎作用。我们的总体目标是 项目是代表显示基于血浆的促炎性内表型的DS的特定亚组 很可能对强效抗炎治疗有反应我们的目标是验证炎症 在DS-AD患者中的内源性表型，并评估AD病理学和神经退行性变的变化， 血浆和神经源性外泌体，在基线和纵向样品。使用Quanterix Simoa平台HD-X分析仪技术以及纳米颗粒跟踪分析仪马尔文NS-300 我们将能够加快目标1和2的进展，克服与大流行病有关的拖延， 以及最大限度地提高高容量，验证技术与增强能力，以实现研究目标。

项目成果

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。

• DOI: 10.1001/jamaneurol.2022.0983
• 发表时间: 2022
• 期刊: JAMA neurology
• 影响因子: 29
• 作者: Rafii,MichaelS;Sol,Olivier;Mobley,WilliamC;Delpretti,Saskia;Skotko,BrianG;Burke,AnnaD;Sabbagh,MarwanN;Yuan,ShaunaH;Rissman,RobertA;Pulsifer,Margaret;Evans,Casey;Evans,ACarol;Beth,Gregory;Fournier,Nicolas;Gray,JulianA

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.

• DOI: 10.1002/dad2.12451
• 发表时间: 2023-04
• 期刊: Alzheimer's & dementia (Amsterdam, Netherlands)