Identifying tinnitus-related genes based on a side-effect network analysis.
Tinnitus, phantom sound perception, is a worldwide highly prevalent disorder for which no clear underlying pathology has been established and for which no approved drug is on the market. Thus, there is an urgent need for new approaches to understand this condition. We used a network pharmacology side-effect analysis to search for genes that are involved in tinnitus generation. We analyzed a network of 1,313 drug-target pairs, based on 275 compounds that elicit tinnitus as side effect and their targets reported in databases, and used a quantitative score to identify emergent significant targets that were more common than expected at random. Cyclooxigenase 1 and 2 were significant, which validates our approach, since salicylate is a known tinnitus generator. More importantly, we predict previously unknown tinnitus-related targets. The present results have important implications toward understanding tinnitus pathophysiology and might pave the way toward the design of novel pharmacotherapies.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e97; doi:10.1038/psp.2013.75; published online 29 January 2014.
1] Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Dr. Héctor N Torres, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina [2] Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
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Elgoyhen
Department of Psychiatry and Psychotherapy, Interdisciplinary Tinnitus Clinic, University of Regensburg, Regensburg, Germany.
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Langguth
Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
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Nowak
Department of Psychiatry and Psychotherapy, Interdisciplinary Tinnitus Clinic, University of Regensburg, Regensburg, Germany.
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Schecklmann
Department of Surgical Sciences, Unit of Neurosurgery, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
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De Ridder
Laboratory for Auditory & Integrative Neuroscience, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, Texas, USA.
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Vanneste