Epidemiology of Narcolepsy Without Cataplexy

不伴猝倒的发作性睡病的流行病学

• 批准号: 7892407
• 负责人: TERRY B Young
• 金额: $ 24.95万
• 依托单位: STANFORD UNIVERSITY
• 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/7892407
• 关键词: Acute; Adherence; Administrator; Adult; Affect; Age; American; Animal Model; Animals; Antigen-Presenting Cells; Anxiety; Autopsy; Biological; Brain; Canis familiaris; Cataplexy; Cells; Cerebrospinal Fluid; Chronic; Clinic; Clinical; Cohort Studies; Communication; Complex; County; Critiques; DNA Library; Data; Data Base Management; Databases; Diagnosis; Diagnostic Procedure; Diagnostic Specificity; Discipline; Disease; Documentation; Ensure; Epidemiology; Evaluation; Event; Excessive Daytime Sleepiness; Foundations; Functional disorder; Funding; General Population; Genes; Goals; Guidelines; HLA Antigens; Health; Heterogeneity; High Prevalence; Histamine; Human; Human Genetics; Hypnagogic Hallucination; Hypoxia; Impaired cognition; Individual; Knowledge; Leadership; Left; Leg; Literature; Maintenance; Measures; Medicine; Modafinil; Modeling; Mood Disorders; Movement; Mus; Narcolepsy; Neuropeptides; Outcome; Participant; Patients; Physiology; Policies; Population; Prevalence; Prevalence Study; Primary Health Care; Principal Investigator; Provider; Publishing; Quality of life; REM Sleep; Rattus; Recruitment Activity; Reporting; Research; Research Personnel; Research Project Grants; Research Proposals; Research Support; Research Training; Resources; Risk Factors; Running; Sampling; Scientist; Seasons; Serum; Signs and Symptoms; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Sleep Paralysis; Snoring; Sodium Oxybate; Specimen; Susceptibility Gene; Symptoms; System; Test Result; Testing; Therapeutic; Time; Tissue Sample; United States National Institutes of Health; Universities; Western Europe; Wisconsin; Woman; Work; Zebrafish; animal colony; base; computerized; data sharing; depression; design; direct application; epidemiology study; human DNA; hypocretin; improved; medical attention; meetings; member; men; middle age; nervous system disorder; neuropathology; neuropsychological; neurotransmission; novel; novel diagnostics; population based; programs; sex; sleep onset; social; web site

During the last 18 years of funding of this program project, the only NIH supported program project focused on narcolepsy, we have made significant strides in understanding the pathophysiology of narcolepsy, as well as the physiology of normal sleep. Our discovery during the last funding period that most cases of human narcolepsy cataplexy are caused by hypocretin (also called orexin) deficiency significantly changed the sleep field. In this revised competitive renewal proposal, based on our recent discoveries, we have refocused our research efforts and recruited new members to expand the expertise of the Center. In this revised proposal, we have brought together a unique group of independent investigators working across disciplines toward a common goal. Based on the reviewers' critiques, we have removed two projects from our original proposal, leaving four projects and a core (Project A). The core (Project A) provides the necessary core resources to support research projects at the Stanford Center for Narcolepsy, most notably biological samples. The goal of Project B, directed by Dr. Terry Young at the University of Wisconsin, Madison is to determine the prevalence of narcolepsy without cataplexy using an epidemiological approach and to study its association with HLA and lypocretin deficiency. Project D, directed by Dr. Juliette Faraco, will use a zebrafish model to isolate novel genes regulating hypocretin and histamine neurotransmission. In Project F, directed by Dr. Luis de Lecea, the discoverer of hypocretins, is seeking to identify novel genes with preferential expression in hypocretin-containing cells; an accessory goal of this project will be to study the neuropathology of narcolepsy without cataplexy. Project E, directed by Dr. Joachim Hallmayer, will use a human genetic approach to identify novel narcolepsy susceptibility genes. Narcolepsy is a frequent and disabling neurological disorder affecting more than 1 in 2,000 Americans. Our recent findings have led to new diagnostic procedures but have not yet changed therapeutic options. Our aims are improved diagnosis, a better understanding of the narcolepsy pathophysiology and the discovery of new treatments, if not a cure for narcoleptic patients.

该项目是 NIH 支持的唯一一个专注于发作性睡病的项目，在过去 18 年的资助期间，我们在理解发作性睡病的病理生理学以及正常睡眠的生理学方面取得了重大进展。我们在上一个资助期间发现，大多数人类发作性睡病猝倒病例是由下丘脑分泌素（也称为食欲素）缺乏引起的，这显着改变了睡眠场。在这份修订后的竞争性更新提案中，根据我们最近的发现，我们重新调整了研究工作的重点，并招募了新成员来扩大中心的专业知识。在这份修订后的提案中，我们聚集了一组独特的独立研究人员，他们跨学科致力于共同目标。根据审稿人的批评，我们从最初的提案中删除了两个项目，留下四个项目和一个核心项目（项目 A）。核心（项目 A）提供必要的核心资源来支持斯坦福发作性睡病中心的研究项目，尤其是生物样本。 B 项目由威斯康星大学麦迪逊分校的 Terry Young 博士领导，其目标是利用流行病学方法确定不伴猝倒的发作性睡病的患病率，并研究其与 HLA 和促胰泌素缺乏的关系。由 Juliette Faraco 博士领导的 D 项目将使用斑马鱼模型来分离调节下丘脑分泌素和组胺神经传递的新基因。在项目 F 中，由下丘脑分泌素的发现者 Luis de Lecea 博士领导，旨在寻找在含有下丘脑分泌素的细胞中优先表达的新基因；该项目的另一个目标是研究不伴有猝倒的发作性睡病的神经病理学。由 Joachim Hallmayer 博士领导的 E 项目将使用人类遗传学方法来识别新型嗜睡症易感基因。发作性睡病是一种常见的致残性神经系统疾病，影响超过二千分之一的美国人。我们最近的发现导致了新的诊断程序，但尚未改变治疗选择。我们的目标是改进诊断、更好地了解发作性睡病的病理生理学以及发现新的治疗方法（即使不能治愈发作性睡病患者）。