ALLFTD: ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration

ALLFTD：ARTFL-LEFFTDS 纵向额颞叶变性

• 批准号: 10916018
• 负责人: Justin Kwan
• 金额: $ 12.21万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10916018
• 关键词: Address; Age; Age of Onset; Alzheimer' s Disease; Alzheimer' s disease related dementia; American; Biological; Biological Markers; C9ORF72; Clinic; Clinical; Clinical Data; Clinical Trials; Clinical assessments; Collection; Communities; Consensus; DNA-Binding Proteins; Data Collection; Development; Diagnosis; Disease; Disease Progression; Enrollment; Evaluation; Familial disease; Family; Fostering; Frontotemporal Dementia; Frontotemporal Lobar Degenerations; Genes; Goals; Health Personnel; Infrastructure; Inherited; Institutional Review Boards; Knowledge; MAPT gene; Molecular Weight; Mutation; Neurodegenerative Disorders; Neurologist; PGRN gene; Participant; Patients; Physicians; Protocols documentation; Recommendation; Recording of previous events; Research; Research Personnel; Research Project Grants; Sampling; Scanning; Scientist; Severity of illness; Study Subject; Syndrome; Training; United States National Institutes of Health; Visit; data sharing; effective therapy; frontotemporal degeneration; imaging study; improved; programs; protein aggregation; symposium; tau Proteins

ARTFL LEFFTDS Longitudinal FTLD: OVERALL SECTION Frontotemporal Lobar Degeneration (FTLD) is the overarching term for a group of neurodegenerative disorders that are believed to be caused by the accumulation of toxic protein aggregates in the CNS, most commonly comprised of one of two major proteinsmicrotubule associated protein tau and TAR DNA binding protein molecular weight 43 kDa. FTLD is at least as common as Alzheimer's disease (AD) in those under the age of 65. Due to the earlier age of onset and the rapid rate of decline, FTLD is thought to have an even greater impact on the lives of patients and families when compared to AD. At least 20% of all FTLD patients have a dominantly inherited familial disorder (f-FTLD), whereas the remaining patients have a sporadic FTLD syndrome (s-FTLD). The current Advancing Research and Treatment in Frontotemporal Degeneration (ARTFL; U54 NS092089) study enrolls and follows these s-FTLD patients. Approximately 50% of f-FTLD is the result of one of three common mutations: the microtubule associated protein tau (MAPT), progranulin (GRN), or chromosome 9 open reading frame 72 (C9orf72) genes. The current Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS; U01 AG045390) study enrolls and follows participants with a known family mutation, while ARTFL also enrolls those with strong family histories but no known mutation. The ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) protocol represents our plan to formalize the merger of the ARTFL and LEFFTDS studies to create an integrated North American research consortium to study FTLD. The ALLFTD program, as implemented through this U19 mechanism, will improve our infrastructure for comprehensive collection and sharing of data through creation of seven cores. We address the main goals recommended by the National Alzheimer's Project Act (NAPA) Steering Committee on the Alzheimer's Disease-Related Dementias (ADRD) focused on FTLD through these cores and two research projects. ALLFTD will support many additional projects that address both the clinical and neuroscientific goals recommended by NAPA ADRD by providing clinical data, scans and biological samples to the scientific community. While there are no effective treatments for any FTLD disorder, increasing numbers of new potential therapies are entering clinical trials. The ALLFTD program's commitment to supporting data collection and sharing with researchers worldwide will foster development of disease-modifying therapies for FTLD. The biological complexity and clinical variability of FTD requires physicians and scientists with a broad range of clinical and scientific expertise, which is brought together by the Neurodegenerative Disorders Clinic. Participants will have clinical assessments, imaging studies, and biospecimen collection to gain knowledge of disease mechanisms and to develop biomarkers to track disease progression. A consensus conference with neurologists, neuropsychologist, and health personnel will take place after the participant visit to discuss the consensus diagnosis and harmonize disease severity rating. All NIH participating investigators have met and completed required protocol specific trainings. The NIH ALLFTD protocol has been approved by the central IRB, and the NIH IRB approval is pending.

ARTFL LEFFTD纵向FTLD：整体段额叶叶变性（FTLD）是一组神经退行性疾病的总体术语，这些疾病被认为是由CN中有毒蛋白聚集物的积累引起的，CNS中的毒性蛋白质聚集物的积累，最常见的是两种主要蛋白质蛋白蛋白蛋白蛋白蛋白蛋白蛋白douubule toune doune doune doun toune toun toune toune coptrub ot 3。 KDA。 FTLD至少与65岁以下患者的阿尔茨海默氏病（AD）一样普遍。由于发病年龄和下降速度的迅速，FTLD被认为对与AD相比，FTLD对患者和家庭的生活产生了更大的影响。至少有20％的FTLD患者患有主要遗传性的家族障碍（F-FTLD），而其余患者患有零星的FTLD综合征（S-FTLD）。当前的额颞变性研究和治疗（ARTFL； U54 NS092089）研究了这些S-FTLD患者。大约50％的F-FTLD是三个常见突变之一的结果：微管相关蛋白TAU（MAPT），progranulin（GRN）或9号染色体9开放式阅读框架72（C9orf72）基因。当前对家族性额颞痴呆受试者（LEFFTDS; U01 AG045390）的纵向评估进行了研究，并跟踪了患有已知家庭突变的参与者，而ARTFL也招募了那些具有强大家庭历史但未知突变的家族病史。 ARTFL LEFFTDS纵向额颞Lobar变性（ALLFTD）方案代表了我们计划正式化ARTFL和LEFFTDS研究的合并，以建立北美综合研究联盟，以研究FTLD。通过这种U19机制实施的AllFTD计划将通过创建七个核心来改善我们的基础架构，以全面收集和共享数据。我们解决了国家阿尔茨海默氏症项目法案（NAPA）指导委员会在阿尔茨海默氏病有关的痴呆症（ADRD）推荐的主要目标，该目标通过这些核心和两个研究项目着重于FTLD。 AllFTD将支持许多其他项目，这些项目通过向科学界提供临床数据，扫描和生物样品来解决NAPA ADRD推荐的临床和神经科学目标。尽管没有针对任何FTLD疾病的有效治疗方法，但越来越多的新潜在疗法正在进入临床试验。 AllFTD计划致力于支持全球研究人员的数据收集和共享，将促进FTLD疾病改良疗法的发展。 FTD的生物复杂性和临床变异性要求具有广泛临床和科学专业知识的医师和科学家，这是由神经退行性疾病诊所汇集在一起​​的。参与者将进行临床评估，成像研究和生物测量收集，以获取有关疾病机制的知识，并开发生物标志物以追踪疾病进展。在参与者访问之后，将与神经系统，神经心理学家和卫生人员进行共识会议，讨论共识诊断并协调疾病严重程度的评级。所有NIH参与的调查人员都已经达到并完成了所需的协议特定培训。 NIH AllFTD协议已得到中央IRB的批准，NIH IRB批准正在等待。