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用于人类嗜睡症诊断试验的血液下丘脑泌素测量。嗜睡症是一种使人衰弱的睡眠障碍，每2000名美国公民中就有1人受到影响。虽然这种疾病的发病最典型地发生在青春期，但诊断通常从疾病发作延迟长达10年。这主要是由于目前没有特定的嗜睡症诊断工具。我们已经发现，下丘脑泌素水平是不可检测的低，在脑脊液（CSF）的大多数患者发作性睡病，cataesthetic。考虑到下丘脑泌素配体和受体的基因消融诱导动物发作性睡病的事实，下丘脑泌素神经传递的缺陷可能是大多数人类发作性睡病的主要病理生理学。在各种睡眠和神经系统疾病中，无法检测到的低CSF下丘脑泌素水平对发作性睡病非常特异，并且CSF下丘脑泌素测量现在被包括在第二版国际睡眠障碍分类（ICSD）中作为发作性睡病-卡他性睡病的阳性诊断。虽然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，下丘脑泌素可以检测到健康受试者的血浆中，但可能是缺乏发作性睡眠受试者。因此，我们将评估血浆测量是否可以用作嗜睡症的替代诊断工具。我们将专注于血浆测定的验证以及更灵敏的血浆测定方法的开发。如果这是成功地实现，中枢下丘脑泌素缺乏症可以测试在睡眠诊所通过常规血液测试。公共卫生相关性：嗜睡症是一种使人衰弱的疾病，每2000名美国公民中就有1人受到影响。我们的初步结果表明，下丘脑泌素可以检测到健康受试者的血浆中，但可能是缺乏发作性睡眠受试者。因此，我们将评估血浆测量是否可用作治疗发作性睡病的替代诊断工具。