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: 7564059
• 负责人: SEIJI NISHINO
• 金额: $ 18.76万
• 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 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7564059
• 关键词: Ablation; Academic achievement; Accounting; Adolescence; Affect; Animals; Antibodies; Arousal; Biological Assay; Blood; Blood Tests; Cataplexy; Cerebrospinal Fluid; Classification; Clinic; Clinical assessments; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Excessive Daytime Sleepiness; Functional disorder; Genetic; Goals; HLA Antigens; Human; Hypothalamic structure; International; Lateral; Ligands; Measurement; Measures; Mediating; Methods; Narcolepsy; Neurologic; Neuropeptides; Onset of illness; Outpatients; Patients; Plasma; Preparation; Principal Investigator; Procedures; Regulation; Research Proposals; Selection for Treatments; Sensitivity and Specificity; Signal Transduction; Sleep; Sleep Disorders; Sleep Wake Cycle; Social Interaction; System; Testing; Validation; base; hypocretin; leukocyte antigen typing; nervous system disorder; neurotransmission; novel diagnostics; programs; public health relevance; receptor; research study; sample collection; tool; treatment response

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一种用于人类发作性睡病诊断测试的血液下丘脑泌素测量方法。嗜睡症是一种使人衰弱的睡眠障碍，每2000名美国人中就有1人受其影响。虽然这种疾病的发病最典型地发生在青春期，但诊断往往延迟至发病后10年。这主要是由于目前没有特定的发作性睡病诊断工具。我们发现大多数嗜睡猝倒患者的脑脊液（CSF）中下丘脑泌素水平低得无法检测。考虑到动物中下丘脑素配体和受体的基因消融可诱发嗜睡症，下丘脑素神经传递的缺陷可能是大多数人类嗜睡症的主要病理生理机制。在各种睡眠和神经系统疾病中，脑脊液下丘脑泌素水平低是嗜睡症的特异性特征，脑脊液下丘脑泌素水平的测定现在已被《国际睡眠障碍分类》（ICSD）第2版纳入嗜睡症-猝厥的阳性诊断。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，如血液测试，将是理想的，特别是在门诊睡眠诊所。我们的初步结果表明，下丘脑泌素可以在健康人的血浆中检测到，但在发作性睡症患者的血浆中可能没有。因此，我们将评估血浆测量是否可以作为发作性睡病的替代诊断工具。我们将重点关注血浆测定法的验证以及更灵敏的血浆测定法的开发。如果成功，中枢下丘脑泌素缺乏症可以在睡眠诊所通过常规血液检查来检测。公共卫生相关性：发作性睡病是一种使人衰弱的疾病，每2000名美国公民中就有1人受其影响。我们的初步结果表明，下丘脑泌素可以在健康人的血浆中检测到，但在发作性睡症患者的血浆中可能没有。因此，我们将评估血浆测量是否可以作为治疗发作性睡病的替代诊断工具。