Complex Neurodegenerative Disorders Clinic

复杂神经退行性疾病诊所

基本信息

批准号：
10916080
负责人：
Justin Kwan
金额：
$ 93.26万
依托单位：
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
依托单位国家：
美国
项目类别：
财政年份：
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/10916080
关键词：
Affect Amyotrophic Lateral Sclerosis Cell physiology Clinic Clinical Clinical Research Clinical assessments Cognitive Collaborations Collection Complex DNA Sequence Alteration Defect Diagnosis Disease Eligibility Determination Epigenetic Process Family Frontotemporal Dementia Functional Imaging Future Gene Mutation Genes Genetic Health Personnel Image Knowledge Laboratories Language Link MAPT gene Molecular Neurodegenerative Disorders Neurologic Symptoms Neurologist Neurology Participant Pathology Patients Physicians Primary Progressive Aphasia Procedures Progressive Supranuclear Palsy Protocols documentation Questionnaires Registries Research Research Personnel Symptoms United States National Institutes of Health Update clinical phenotype cognitive testing corticobasal syndrome gene product individual patient interest molecular imaging motor symptom multidisciplinary mutant phenomenological models precision medicine protein TDP-43 research clinical testing research study symposium

项目摘要

Although neurodegenerative disorders were historically considered as discrete diseases, this concept has been challenged by scientific discoveries showing overlapping clinical symptoms, genes, and pathology. Neurodegenerative disorders associated with the intracellular aggregation of misfolded TDP-43 or microtubule-associated tau proteins may present with a mixture of cognitive, language, and motor symptoms. Patients may be diagnosed with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), or primary progressive aphasia (PPA). Some causative genes have been found for each disorder, although most patients have sporadic disease. Interestingly, the same genetic mutation can produce different clinical phenotypes. The link between the gene mutations and pathology in these disorders may lie in the molecular and cellular processes affected by mutant gene products. As the field of neurology moves more towards the molecular characterization of neurodegenerative disorders, there is a need to understand clinical phenomenology in the context of pathology and genetic or epigenetic defects that are the drivers of disease. Given the broad spectrum of neurological symptoms in this family of disorders, this clinic brings together an outstanding and energetic group of physicians and researchers with a wide range of clinical expertise and scientific approaches. Patients undergo clinical and cognitive assessments, imaging, and collection of biospecimens for research studies. The objective is to gain knowledge that will set the stage for precision medicine in which therapy is tailored to the underlying cause of each patient's disease. The Complex Neurodegenerative Disorders Clinic continues to operate smoothly in FY 2023. The staff of the clinic arrange clinical studies that help to establish the diagnosis, as well as a standard battery of clinical and cognitive testing. Biospecimens from participants are collected for research purposes and shared with collaborators. Each month, the clinic holds a multidisciplinary conference with neurologists, neuropsychologists, and health personnel involved in the clinic to discuss individual patients and their diagnosis and suitability for research protocols. Patients who are found to be eligible for ongoing research studies are referred to those studies. 7 tesla imaging has been added as a new research procedure in collaboration with Laboratory of Functional & Molecular Imaging and select participants will undergo this procedure. Participants may sign up for a registry for receiving information on future NIH studies and an annual questionnaire to update their current status and continued interest in research.

尽管神经退行性疾病在历史上被认为是离散疾病，但该概念受到了科学发现的挑战，表现出重叠的临床症状，基因和病理。与错误折叠的TDP-43或微管相关的TAU蛋白的细胞内聚集有关的神经退行性疾病可能会带有认知，语言和运动症状的混合物。患者可能被诊断出患有肌萎缩性侧索硬化症（ALS），额颞痴呆（FTD），皮质型综合征（CBS），进行性性核上麻痹（PSP）或原发性进行性疾病（PPA）。尽管大多数患者患有零星疾病，但已经发现了每种疾病的一些病因基因。有趣的是，相同的遗传突变可以产生不同的临床表型。这些疾病中的基因突变与病理之间的联系可能在于受突变基因产物影响的分子和细胞过程。随着神经学领域的发展越来越多，在神经退行性疾病的分子表征上，有必要在病理学以及遗传或表观遗传缺陷的背景下理解临床现象学。鉴于该疾病家族中的各种神经系统症状，该诊所汇集了一群出色而充满活力的医师和研究人员，具有广泛的临床专业知识和科学方法。患者接受临床和认知评估，成像和生物测量的收集进行研究。目的是获取知识，这将为精确医学奠定阶段，在这些医学中，在这种医学上是针对每个患者疾病的根本原因量身定制的。复杂的神经退行性疾病诊所在2023财年继续顺利运作。诊所的工作人员安排临床研究，有助于确定诊断，以及一系列标准的临床和认知测试。为了研究目的，收集了参与者的生物测量，并与合作者共享。每个月，该诊所与诊所参与的神经系统，神经心理学家和卫生人员进行跨学科会议，讨论个别患者及其对研究方案的诊断和适合性。被认为有资格进行正在进行的研究的患者被称为这些研究。 7特斯拉成像已作为与功能和分子成像实验室合作的新研究程序添加，并且选定的参与者将接受此程序。参与者可以签署注册表，以接收有关未来NIH研究的信息和一份年度问卷，以更新其当前状态并继续对研究感兴趣。