Kidney Multiphoton Analysis of Therapeutic Agents

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DESCRIPTION (provided by applicant): The rate of drug development is disappointingly slow, in part because of the failure of preclinical drug studies to elucidate the mechanisms of drug actions. INphoton has demonstrated that intravital microscopy can be used as a powerful tool in preclinical drug studies, providing the mechanistic insights typically associated with studies of cultured cells, but in the physiologically relevant context of the intact animal. Here we propose to develop an integrated set of quantitative intravital microscopy assays of renal toxicity, an undesired side-effect of a large number of candidate drug compounds. These assays will be developed using well-established models of renal toxicity in the context of both acute and chronic renal injury. This project will result in the development of unique research tools that can be used to complement and extend traditional ADME-tox approaches in ways that will expedite drug development. These tools will significantly extend INphoton's capabilities and market, providing the first step in the wide-scale commercialization of INphoton's intravital microscopy services, which will ultimately include capabilities for analyses of other organ systems and of in vivo tumor biology. PUBLIC HEALTH RELEVANCE: INphoton, LLC will commercialize intravital microscopy of the kidney as a contract research service to be used as an investigational tool for preclinical drug development. The high resolution provided by this approach provides unique mechanistic insights into the cellular processing and physiological effects of candidate drug compounds, thereby expediting drug development.