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; 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）：这项修订的建议的主要目标是为人类性睡病进行诊断测试建立血液降压素措施。睡病是一种使人衰弱的睡眠障碍，影响2000年美国公民1。尽管该疾病的发作通常最常发生在青春期，但诊断通常会延迟到10年以来疾病发作。这主要是由于目前没有特定的麻醉症诊断工具。我们已经发现，大多数发作性发育迟发性 - 尾囊肿的患者的脑脊液（CSF）中低封素的水平不高。考虑到低载素配体和受体的遗传消融诱导动物中的发病疗法的事实，低载素神经传递的缺陷很可能是大多数人类麻醉症的主要病理生理学。不可思议的低CSF降压素水平非常特异性对于各种睡眠和神经系统疾病中的麻醉症，现在将CSF降压素措施作为阳性诊断在国际睡眠障碍（ICSD）的第二修订中，作为对Narcolepsy-cataplexy的阳性诊断。尽管许多患者可能会从这项新的诊断测试中获得好处，但侵入性较小的方法的发展是理想的，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低载素，但在麻醉受试者中可能不存在。因此，我们将评估是否可以将血浆测量用作发作性睡病的替代诊断工具。我们将重点介绍血浆测定的验证以及更敏感的血浆测量测定法。如果成功实现这一目标，则可以通过常规的血液测试在睡眠诊所中测试中枢性低载素缺乏症。公共卫生相关性：睡病是一种使人衰弱的疾病，影响了2000年美国公民。我们的初步结果表明，可以在健康受试者的血浆中检测到低载素，但在麻醉受试者中可能不存在。因此，我们将评估是否可以将血浆测量用作用于治疗发作性睡病的替代诊断工具。