The Mayo Clinic Center for Individualized Treatment of Alcohol Dependence

描述（由申请人提供）：梅奥诊所酒精依赖个体治疗中心（CITA）是P20探索性/发展性酒精研究中心提案，其总体主题是使用转化研究策略创建一个新的研究中心，有能力发起和开展药物基因组学探针研究，以区分严重酒精依赖患者的治疗反应。这个新中心将建立在一个现有的研究团队的基础上，该团队在一个主要的学术医学中心进行协同临床和临床前转化研究，该中心的资源已经用于提供个性化临床护理的转化研究和培训。能够为酒精依赖提供个性化医疗治疗这一目标的重要性日益明显。这在识别抗屈光性药物的可变反应方面尤其正确。虽然有些人的反应很好，但显然有很多人没有。能够可靠地区分那些对有效治疗有反应的人的能力有多重好处。有效识别治疗反应者将大大节省费用和个人痛苦。另一个潜在的好处是开发具有非常有针对性适应症的新药物，这将对那些可以通过低成本基因分型识别的特定个体有独特的帮助。建立这种创新方法来研究酒精治疗的可行性取决于P20中心的研究人员与目前作为药物基因组学研究网络团队（PGRN）和高级基因组学技术中心（AGTC）的一部分工作的科学家之间的密切合作。此外，梅奥诊所转化科学活动中心（CTSA）的广泛资源将为利用最先进的基因分型技术建立转化研究提供坚实的基础。描述了四个探索性项目，以促进从临床前到临床研究的转化。两个项目探讨遗传变异和对环境的反应之间的关系。第一项研究使用小鼠模型，而第二项研究是药物基因组学探针研究，使用前瞻性定义的酒精依赖受试者样本。其余两个项目使用磁共振波谱来探索中枢神经系统中谷氨酸浓度与阿坎普罗酸治疗小鼠和酒精依赖患者之间的关系。

DESCRIPTION (provided by applicant): The Mayo Clinic Center for the Individual Treatment of Alcohol Dependence (CITA) is a P20 exploratory/ developmental alcohol research center proposal with the over-arching theme of using translational research strategies to create a new research center with the capacity to originate and conduct pharmacogenomic probe studies to differentiate treatment responses in patients with severe alcohol dependence. This new center would build upon an already existing team of researchers conducting synergistic clinical and preclinical translational research in a major academic medical center with resources already devoted to translation research and training in the provision of individualized clinical care. The importance of the goal of being able to provide individualized medical treatment for alcohol dependence has become increasingly apparent. This is specifically true related to the identification of variable responses to antidipsotropic medications. Whereas some individuals have excellent responses, there are clearly many who do not. The ability to be able to reliably differentiate those who will respond to an effective treatment has multiple benefits. The efficient identification of treatment responders would result in enormous saving of both cost and personal suffering. Another potential benefit would be the development of new medications with very targeted indications that would be uniquely helpful for selected individuals who could be identified by low cost genotyping. The feasibility of establishing this innovative approach to the study of alcohol treatment is dependent on close collaboration between the investigators of the P20 Center and the scientists who are currently working as part of the Pharmacogenomic Research Network team (PGRN) and the Advanced Genomic Technology Center (AGTC). Additionally, the broad resources of the Center for Translational Science Activities (CTSA) at the Mayo Clinic will provide a strong foundation from which to build translational research studies utilizing state-of-the-art genotyping technology. Four exploratory projects are described that foster translation from preclinical to clinical investigations. Two projects explore the relationship between genetic variation and response to acamprosate administration. The first uses a mouse model while the second is a pharmacogenomic probe study using a prospectively defined sample of subjects with alcohol dependence. The remaining two projects use magnetic resonance spectroscopy to explore the relationship between glutamate concentrations in the central nervous system and acamprosate treatment in mice and in patients treated for alcohol dependence.