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）：大量饮酒很常见，并带来了重大的社会/经济挑战。尽管长期使用少量酒精并不总是有害，但使用较重（> 2饮料/天）通常是有害的，并且经常导致酒精中毒 - 最常见的形式是酒精滥用（AA）和酒精依赖（AD）。 AA/AD影响约25％的美国人口，造成近20​​00亿美元/年的经济损害和人类苦难。如果发现酒精滥用较早，这些不良后果是可以避免的。但是，当前的慢性酒精使用筛查方法仅在测试前的几个小时内捕获酒精的使用或依赖不敏感的非特异性蛋白质分析。一种可以更可靠地识别慢性酒精滥用和监测禁欲的下一代方法对包括医疗，政府，安全和运输机构在内的许多团体都具有极大的兴趣。行为诊断的总体目标是开发，验证和商业化这样的下一代技术。在此阶段的I阶段可行性研究中，我们将基于我们在物质使用表观遗传学方面的丰富经验，并寻求实现两个目标。首先，我们将明确地证明与饮酒相关的甲基化的总体模式是可靠的。其次，我们将在没有立即饮酒的情况下确定DNA甲基化的稳定性。在此阶段I项目中，我们建议通过首先验证与酒精相关的DNA甲基化变化的先前全基因组分析的结果，通过比较戒烟控制的甲基化谱与接受急性排毒的重饮酒者的甲基化曲线。然后，我们将跟随这些饮酒者进行30天的住院治疗停留和检查甲基化的甲基化，并在住院保证保证30天后，以最显着差异化的甲基化残留物来确定哪些稳定（特质标记）（特质标记），哪些开始恢复到人群平均值（状态标记和可能的治疗指标相关的相关剂量指标）。如果成功的话，该项目将是该领域的重大进步，并将作为我们II期开发的原理证明，用于用于检测和定量慢性酒精使用和监测出院后患者的禁欲。这项高度创新的建议是重要的，因为针对这些疾病的易于使用的，相对万无一失的诊断测试的发展可能会在医疗，民用和法医应用中得到广泛接受。该公司为进行研究做好了充分的准备。首先，Philibert博士是该技术的共同发入者，是一名经过认证的精神科医生，在拟议的研究的各个方面都有丰富的经验，并且具有监督本研究的任何潜在阶段II的直接能力。其次，首席执行官奥斯本（Osborn）博士在生物行业有30年的经验，并且与生物医学和生物爱好社区有很好的联系。第四，我们得到了伦理学家和药物使用专家团队的进一步帮助。第四，该公司就该技术和其他相关技术获得了知识产权的权利。