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.
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