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.

增刊摘要 几乎所有的唐氏综合征(DS)患者都表现出加速的神经病理和认知损害 随着年龄的增长，最终会发展为阿尔茨海默病(AD)。不管这么多人 尽管DS的研究取得了很大进展，但我们对DS患者的AD治疗仍缺乏实质性的了解。在这 作为补充，我们建议使用我们建立的 来自之前完成的临床试验的生物库样本中的促炎内表型分析， “老年唐氏综合症患者的维生素E。”这项研究将使我们了解它们之间的相互关系 在DS-AD患者的免疫信号之间。此外，还将协助如何将这些点连接起来 盛行的免疫信号可能影响AD生物标志物的抗炎作用。我们的总体目标是 项目是代表DS的一个特定亚群，显示基于血浆的促炎内表型 最有可能对有效的抗炎疗法有反应。我们的目标是验证炎症性 DS-AD患者的内表型和评估AD病理和神经变性的变化 血浆和神经来源的外切体，包括基线和纵向样本。利用Quanterix SiMoA平台HD-X分析仪技术以及马尔文NS-300纳米粒子跟踪分析仪 通过这项文书，我们将能够加快目标1和目标2的进展，以克服与大流行有关的延误，因为 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

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)