Diagnostic Values of Plasma Hypocretin Measures for Sleep Disorders

血浆下丘脑分泌素测量对睡眠障碍的诊断价值

• 批准号: 7469299
• 负责人: SEIJI NISHINO
• 金额: $ 22.52万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-05 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7469299
• 关键词: Ablation; Academic achievement; Accounting; Adolescence; Affect; Animals; Antibodies; Arousal; Biological Assay; Blood; Blood Tests; Cataplexy; Cerebrospinal Fluid; Classification; Clinic; Clinical assessments; Condition; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Excessive Daytime Sleepiness; Functional disorder; Genetic; Goals; HLA Antigens; Human; Hypothalamic structure; International; Invasive; Lateral; Ligands; Measurement; Measures; Mediating; Methods; Narcolepsy; Neurologic; Neuropeptides; Onset of illness; Outpatients; Patients; Plasma; Preparation; Principal Investigator; Procedures; Public Health; Regulation; Research Proposals; Selection for Treatments; Sensitivity and Specificity; Signal Transduction; Sleep; Sleep Disorders; Sleep Wake Cycle; Social Interaction; System; Testing; Validation; base; human study; hypocretin; leukocyte antigen typing; nervous system disorder; neurotransmission; novel diagnostics; programs; receptor; research study; response; sample collection; tool

DESCRIPTION (provided by applicant): The principal goal of this revised proposal is to establish a blood hypocretin measure for a diagnostic test for human narcolepsy. Narcolepsy is a debilitating sleep disorder that affects 1 in 2000 U.S. citizens. Although the onset of the disease most typically occurs in adolescence, the diagnosis is often delayed by up to 10 years from the disease onset. This is mainly due to the fact that no specific diagnostic tool of narcolepsy is currently available. We have discovered that hypocretin levels are undetectably low in the cerebrospinal fluid (CSF) of most patients with narcolepsy-cataplexy. Considering the fact that genetic ablations of the hypocretin ligand and receptors induce narcolepsy in animals, deficits in hypocretin neurotransmission is likely to be the major pathophysiology of most human narcolepsy. Undetectably low CSF hypocretin levels are very specific for narcolepsy among various sleep and neurological disorders, and CSF hypocretin measures are now included as a positive diagnosis of narcolepsy-cataplexy in the 2nd revision of International Classification of Sleep Disorders (ICSD). Although many patients will likely receive benefits from this new diagnostic test, development of less invasive-methods, such as blood testing would be ideal, especially at outpatient sleep clinics. Our preliminary results suggest that hypocretin can be detected in the plasma of healthy subjects, but may be absent in narcoleptic subjects. We therefore will evaluate whether plasma measurement can be used as an alternative diagnostic tool for narcolepsy. We will focus on the validation of the plasma assay as well as the development of more sensitive assays for plasma measurement. If this is successfully achieved, central hypocretin deficiency can be tested for at sleep clinics by a routine blood test. PUBLIC HEALTH RELEVANCE: Narcolepsy is a debilitating disorder that affects 1 in 2000 U.S. citizens. Our preliminary results suggest that hypocretin can be detected in the plasma of healthy subjects, but may be absent in narcoleptic subjects. We will therefore evaluate whether a plasma measurement can be used as an alternative diagnostic tool for the treatment of narcolepsy.

描述（由申请人提供）：本修订提案的主要目标是建立血液下丘脑分泌素测量方法，用于人类发作性睡病的诊断测试。发作性睡病是一种使人衰弱的睡眠障碍，每 2000 名美国公民中就有 1 人患有发作性睡病。尽管该疾病最常发病于青春期，但诊断往往会延迟至发病后长达 10 年。这主要是因为目前还没有发作性睡病的特异性诊断工具。我们发现，大多数发作性睡病猝倒患者的脑脊液 (CSF) 中下丘脑分泌素水平低得无法检测。考虑到下丘脑分泌素配体和受体的基因消除会诱发动物的嗜睡症，下丘脑分泌素神经传递缺陷可能是大多数人类嗜睡症的主要病理生理学。无法检测到的低脑脊液下丘脑分泌素水平对于各种睡眠和神经系统疾病中的发作性睡病非常特异，并且脑脊液下丘脑分泌素测量现已被纳入国际睡眠障碍分类 (ICSD) 第二次修订中，作为发作性睡病猝倒症的阳性诊断。尽管许多患者可能会从这种新的诊断测试中受益，但开发侵入性较小的方法（例如血液测试）将是理想的选择，尤其是在门诊睡眠诊所。我们的初步结果表明，可以在健康受试者的血浆中检测到下丘脑分泌素，但在发作性睡病受试者中可能不存在。因此，我们将评估血浆测量是否可以用作发作性睡病的替代诊断工具。我们将重点关注血浆测定的验证以及更灵敏的血浆测量测定的开发。如果成功实现这一点，则可以在睡眠诊所通过常规血液检查来检测中枢性下丘脑分泌素缺乏症。公共卫生相关性：发作性睡病是一种使人衰弱的疾病，影响每 2000 名美国公民中就有 1 人患有嗜睡症。我们的初步结果表明，可以在健康受试者的血浆中检测到下丘脑分泌素，但在发作性睡病受试者中可能不存在。因此，我们将评估血浆测量是否可以用作治疗发作性睡病的替代诊断工具。