Clinical trials to prevent Alzheimer's Disease in Down Syndrome
预防唐氏综合症中阿尔茨海默病的临床试验
基本信息
- 批准号:10700138
- 负责人:
- 金额:$ 228.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-15 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease therapeuticAlzheimer&aposs disease therapyAlzheimer’s disease biomarkerAmyloidAmyloid beta-ProteinAmyloid beta-Protein PrecursorAwardBiological MarkersBrainCause of DeathChromosome 21ClinicalClinical TrialsClinical assessmentsCognitiveCollaborationsConduct Clinical TrialsCongenital chromosomal diseaseDataDementiaDiseaseDisease MarkerDisease ProgressionDouble-Blind MethodDown SyndromeEnrollmentEthicsEuropeanExhibitsFundingFutureGene ProteinsGeneral PopulationGenesGeneticHippocampusImageImmunotherapyImpaired cognitionIndividualInfrastructureIntellectual functioning disabilityLinkLiquid substanceMagnetic Resonance ImagingMeasuresMethodsModificationMonitorMutationNeurofibrillary TanglesOutcome MeasureParticipantPathogenesisPathway interactionsPersonsPhasePlacebo ControlPlacebosPlasmaPlayPopulationPositron-Emission TomographyProceduresRandomizedRoleRunningSafetySenile PlaquesSiteTherapeuticTherapeutic Clinical TrialTherapeutic TrialsTreatment outcomeUnited States National Institutes of Healthbrain volumeclinical trial readinesscohortdata managementdementia riskdouble-blind placebo controlled trialelectronic data capture systemexperienceimprovedlifetime riskmRNA Expressionneuropathologynon-dementedperformance sitephase II trialpreventprogression markerprotein expressiontau Proteinstrial readinessworking group
项目摘要
PROJECT SUMMARY/ABSTRACT
The discovery that individuals with Trisomy 21, or Down syndrome (DS) have neuropathological
features identical to those with sporadic Alzheimer's disease (AD) played a critical role in the
identification of the amyloid precursor protein gene on chromosome 21 supporting the amyloid
cascade hypothesis. People with DS have a lifetime risk for dementia in excess of 75% and
comprise the world's largest population of genetically-determined AD. Just as studying DS
helped identify the role of amyloid precursor protein mutations in AD pathogenesis, it is also
likely to inform us of the potential benefit of manipulating the amyloid pathway on treatment
outcomes in AD. It is critically important to the DS population and to the AD therapeutics field to
conduct clinical trials, particularly those targeting amyloid accumulation, in individuals with DS.
With this application, we propose to utilize the existing depth and breadth of expertise of the
NIA-funded Alzheimer's Clinical Trial Consortium (ACTC) to conduct AD clinical trials in adults
with DS across performance sites with expertise in DS including the Alzheimer's Biomarker
Consortium for Down Syndrome (ABC-DS). As part of an NIH award received last year, we
established the ACTC-DS network which includes working groups comprised of leaders from
ACTC, ABC-DS and the European Horizon21 DS network to develop the collaborations,
infrastructure and plans required to conduct AD clinical trials in DS.
During the proposed R61 `Trial Readiness Phase' of the present project, in Aim 1, we will enroll
120 adults with DS (ages 35-55) across 15 sites into a trial ready cohort (TRC) to collect
outcome measures and biomarkers harmonized with those being collected in the ongoing ABC-
DS study (n = ~400). In Aim 2, we will determine the relationships between cognitive measures
and AD biomarkers to identify endpoints for clinical trials that best reflect disease progression.
During the R33 `Clinical Trial' phase, for Aim 3, we propose to implement a phase II
randomized, double-blind, placebo-controlled trial to evaluate the safety and tolerability of a
promising anti-amyloid therapeutic among individuals the TRC. In Aim 4, we will determine the
impact of this agent on biomarker evidence of disease modification.
Fundamentally, this project will serve to bring AD therapies to the DS population by leveraging
the infrastructure of ACTC and incorporating the experience and expertise of the ABC-DS and
Horizon21 networks. Beyond the proposed trial, this will establish the means and methods to
conduct future therapeutic trials in this population. The potential impact of this approach on
improving the lives of adults with DS as well as the general population cannot be overstated.
项目总结/摘要
发现患有21三体或唐氏综合征(DS)的个体具有神经病理学
与散发性阿尔茨海默病(AD)相同的特征在阿尔茨海默病中起着关键作用。
21号染色体上支持淀粉样蛋白的淀粉样前体蛋白基因的鉴定
级联假说患有DS的人一生中患痴呆症的风险超过75%,
包括世界上最大的遗传决定的AD人群。就像学习DS一样
有助于确定淀粉样前体蛋白突变在AD发病机制中的作用,
可能告诉我们操纵淀粉样蛋白通路对治疗的潜在益处
AD的结果。对于DS人群和AD治疗领域来说,
进行临床试验,特别是那些针对淀粉样蛋白积累的个人与DS。
通过这项申请,我们建议利用现有的专业知识的深度和广度,
美国国家情报局资助的阿尔茨海默氏症临床试验联盟(ACTC)在成人中进行AD临床试验
与具有DS(包括阿尔茨海默氏症生物标志物)专业知识的绩效研究中心的DS合作
唐氏综合症联盟(ABC-DS)。作为去年获得的NIH奖的一部分,我们
建立了ACTC-DS网络,其中包括由来自以下国家的领导人组成的工作组:
ACTC,ABC-DS和欧洲地平线21 DS网络,以发展合作,
在DS中进行AD临床试验所需的基础设施和计划。
在本项目拟议的R61“试验准备阶段”期间,在目标1中,我们将招募
15个研究中心的120名DS成人(年龄35-55岁)进入试验就绪队列(TRC),以收集
结果指标和生物标志物与正在进行的ABC中收集的指标和生物标志物相协调-
DS研究(n = ~400)。在目标2中,我们将确定认知测量之间的关系
和AD生物标志物,以确定最能反映疾病进展的临床试验终点。
在R33“临床试验”阶段,为了实现目标3,我们建议实施第二阶段
一项随机、双盲、安慰剂对照试验,旨在评估
在个体中有希望的抗淀粉样蛋白治疗剂TRC。在目标4中,我们将确定
该试剂对疾病修饰生物标志物证据的影响。
从根本上说,该项目将通过利用
ACTC的基础设施,并结合ABC-DS的经验和专业知识,
地平线21网络。除了拟议的试验之外,这将建立手段和方法,
在这个人群中进行未来的治疗试验。这一做法的潜在影响
改善成年DS患者和普通人群的生活不能被夸大。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Michael S Rafii其他文献
Recent developments in Alzheimer's disease therapeutics
阿尔茨海默病治疗学的最新进展
- DOI:
10.1186/1741-7015-7-7 - 发表时间:
2009-02-19 - 期刊:
- 影响因子:8.300
- 作者:
Michael S Rafii;Paul S Aisen - 通讯作者:
Paul S Aisen
Addressing challenges in health care and research for people with Down syndrome
应对唐氏综合征患者医疗保健和研究方面的挑战
- DOI:
10.1016/s0140-6736(24)00478-1 - 发表时间:
2024-05-11 - 期刊:
- 影响因子:88.500
- 作者:
Juan Fortea;Eimear McGlinchey;Joaquín M Espinosa;Michael S Rafii - 通讯作者:
Michael S Rafii
The amyloid clock: mapping Alzheimer's disease in Down syndrome
淀粉样蛋白时钟:绘制唐氏综合征中的阿尔茨海默病图谱
- DOI:
10.1016/s1474-4422(24)00437-x - 发表时间:
2024-12-01 - 期刊:
- 影响因子:45.500
- 作者:
Michael S Rafii - 通讯作者:
Michael S Rafii
Michael S Rafii的其他文献
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{{ truncateString('Michael S Rafii', 18)}}的其他基金
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:
10296249 - 财政年份:2021
- 资助金额:
$ 228.73万 - 项目类别:
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 - 财政年份:2021
- 资助金额:
$ 228.73万 - 项目类别:
Clinical trials to prevent Alzheimer's Disease in Down Syndrome
预防唐氏综合症中阿尔茨海默病的临床试验
- 批准号:
9893363 - 财政年份:2019
- 资助金额:
$ 228.73万 - 项目类别:
Clinical trials to prevent Alzheimer's Disease in Down Syndrome
预防唐氏综合症中阿尔茨海默病的临床试验
- 批准号:
10249007 - 财政年份:2019
- 资助金额:
$ 228.73万 - 项目类别:
Clinical trials to prevent Alzheimer's Disease in Down Syndrome
预防唐氏综合症中阿尔茨海默病的临床试验
- 批准号:
10017144 - 财政年份:2019
- 资助金额:
$ 228.73万 - 项目类别:
Clinical trials to prevent Alzheimer's Disease in Down Syndrome
预防唐氏综合症中阿尔茨海默病的临床试验
- 批准号:
10689370 - 财政年份:2019
- 资助金额:
$ 228.73万 - 项目类别:
ACTIVE IMMUNOTHERAPY FOR COGNITIVE DECLINE IN ADULTS WITH DOWN SYNDROME
积极免疫疗法治疗成人唐氏综合症认知能力下降
- 批准号:
8750445 - 财政年份:2014
- 资助金额:
$ 228.73万 - 项目类别:
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