Using DNA Methylation to Determine Recent Alcohol Consumption Patterns

利用 DNA 甲基化确定近期的饮酒模式

• 批准号: 8452381
• 负责人: Terry W Osborn
• 金额: $ 16.79万
• 依托单位: BEHAVIORAL DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-15 至 2014-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8452381
• 关键词: Abstinence; Acute; Address; Admission activity; Affect; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcoholic beverage heavy drinker; Alcoholism; Alcohols; Algorithms; Behavioral; Biological Assay; Blood specimen; Cannabis; Chronic; Communities; DNA; DNA Methylation; Data; Detection; Development; Diagnostic; Diagnostic tests; Disease; Economics; Epigenetic Process; Ethicists; Ethnic Origin; Feasibility Studies; Forensic Medicine; Funding; Generations; Goals; Heavy Drinking; Histocompatibility Testing; Hour; Human; Industry; Inpatients; Intellectual Property; Laboratories; Lead; Legal patent; Licensing; Lymphocyte; Measures; Medical; Methods; Methylation; Monitor; Nicotine; Patients; Pattern; Phase; Population; Process; Property Rights; Proteins; Psychiatrist; Publishing; Resources; Sampling; Secure; Security; Small Business Innovation Research Grant; Specialist; Spottings; Staging; Supervision; Technology; Testing; Transportation; Validation; Work; adverse outcome; age group; alcohol abstinence; alcohol abuse therapy; alcohol monitoring; chronic alcohol ingestion; clinical decision-making; computerized; detoxication; drinking; experience; genome wide association study; genome-wide; genome-wide analysis; innovation; interest; male; neuropsychiatry; new technology; next generation; phase 1 study; phase 2 study; problem drinker; public health relevance; research and development; research clinical testing; screening; social; stability testing; tool; trait; treatment program

DESCRIPTION (provided by applicant): Heavy alcohol use is common and presents a major social/economic challenge. Although chronic use of small amounts of alcohol is not always harmful, heavier use (>2 drinks/day) is generally harmful and frequently leads to alcoholism-the most common forms being alcohol abuse (AA) and alcohol dependence (AD). AA/AD affect ~25% of the U.S. population and cause nearly $200 billion/yr of economic damage and untold human misery. These adverse outcomes are potentially avoidable if the alcohol abuse is spotted early; however, current screening methods for chronic alcohol use capture alcohol usage only in the hours prior to testing or rely on insensitive, non-specific protein assays. A next-generation method that could more reliably identify chronic alcohol abuse and monitor abstinence would be of great interest to a large number of groups, including medical, governmental, security and transportation agencies. Developing, validating, and commercializing such a next-generation technology is Behavioral Diagnostic's overall goal. In this Phase I feasibility study, we will build upon our extensive experience in substance use epigenetics and will seek to achieve two goals. First, we will unequivocally demonstrate that the overall patterns of methylation associated with alcohol use are reliable. Second, we will determine the stability of DNA methylation in the absence of immediate alcohol use. In this Phase I project, we propose to do this by first validating the results from a prior genome-wide analysis of alcohol associated DNA methylation changes by comparing the methylation profiles of abstinent controls with that of heavy drinkers admitted for acute detoxication. We will then follow these drinkers through a 30 day inpatient treatment stay and check methylation at the most significantly differentially methylated residues after 30 days of inpatient assured abstinence to determine which are stable (trait marker) and which start the process of reverting to the population mean (state marker and possible indicator of treatment associated abstinence). If successful, this project will be a significant advancement for the field and will serve as proof of principle for our Phase II development of a full-scale diagnostic tool for both the detection and quantitation of chronic alcohol use and monitor abstinence in patients after discharge. This highly innovative proposal is significant because the development of easy to use, relatively foolproof diagnostic tests for these disorders could find widespread acceptance in medical, civil and forensic applications. The company is well prepared to conduct the studies for several reasons. First, Dr. Philibert, is a co-inventor of the technology, is a board certified psychiatrist with extensive experience in all aspects of the proposed studies , and has direct capability of overseeing any potential Phase II of this study. Second, Dr. Osborn, the CEO, has thirty years of experience in bio-industry and is well connected to the biomedical and bioventure communities. Fourth, we are further aided by a team of ethicists and substance use specialists. Fourth, the company has secured intellectual properties rights with respect to this and other related technologies.

描述(由申请人提供)：酗酒很常见，是一个重大的社会/经济挑战。虽然长期少量饮酒并不总是有害的，但过量饮酒(每天2杯)通常是有害的，并经常导致酒精中毒--最常见的形式是酒精滥用(AA)和酒精依赖(AD)。AA/AD影响大约25%的美国人口，每年造成近2000亿美元的经济损失和数不清的人类苦难。如果及早发现酗酒，这些不良后果可能是可以避免的；然而，目前的慢性酒精使用筛查方法只能在测试前几个小时捕获饮酒情况，或者依赖不敏感、非特异性的蛋白质分析。下一代方法可以更可靠地识别慢性酒精滥用并监测戒酒情况，这将引起包括医疗、政府、安全和交通机构在内的大量团体的极大兴趣。开发、验证和商业化这种下一代技术是行为诊断公司的总体目标。在这项第一阶段的可行性研究中，我们将以我们在物质使用表观遗传学方面的丰富经验为基础，并将寻求实现两个目标。首先，我们将毫不含糊地证明与酒精使用相关的甲基化的总体模式是可靠的。其次，我们将确定在没有立即饮酒的情况下DNA甲基化的稳定性。在这个第一阶段的项目中，我们建议首先验证先前对酒精相关DNA甲基化变化的全基因组分析的结果，方法是比较戒酒对照组和因急性戒毒而入院的酗酒者的甲基化情况。然后，我们将跟踪这些饮酒者进行30天的住院治疗，并检查在住院保证戒酒30天后，最显著差异的甲基化残留物的甲基化情况，以确定哪些是稳定的(特征标记)，哪些开始恢复到总体平均水平(状态标记和可能的治疗与戒酒相关的指标)。如果成功，该项目将是该领域的重大进步，并将成为我们第二阶段开发全面诊断工具的原则证明，该工具用于检测和量化慢性酒精使用并监测患者出院后的戒酒情况。这一极具创新性的建议意义重大，因为开发易于使用、相对万无一失的这些疾病的诊断测试可以在医疗、民事和法医应用中得到广泛接受。出于几个原因，该公司已经做好了进行研究的准备。首先，菲利伯特博士是这项技术的共同发明者之一，是一名获得委员会认证的精神病学家，在拟议研究的所有方面都有丰富的经验，并有直接能力监督这项研究的任何潜在的第二阶段。其次，首席执行官奥斯本博士在生物行业拥有30年的经验，并与生物医学和生物风险投资社区建立了良好的联系。第四，我们还得到了伦理学家和物质使用专家团队的进一步帮助。第四，该公司获得了这项技术和其他相关技术的知识产权。