Otology & Neurotology

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Otology & Neurotology:
doi: 10.1097/MAO.0000000000000254
Sensorineural Hearing Loss & Tinnitus

Metabolomic and Network Analysis of Pharmacotherapies for Sensorineural Hearing Loss

Muurling, Tjeerd*†; Stankovic, Konstantina M.*

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Hypothesis: Different pharmacotherapies for sensorineural hearing loss (SNHL) are interconnected in metabolic networks with molecular hubs.

Background: Sensorineural hearing loss is the most common sensory deficit worldwide. Dozens of drugs have shown efficacy against SNHL in animal studies and a few in human studies. Analyzing metabolic networks that interconnect these drugs will point to and prioritize development of new pharmacotherapies for human SNHL.

Methods: Drugs that have shown efficacy in treating mammalian SNHL were identified through PubMed literature searches. The drugs were analyzed using the metabolomic analysis and the “grow-tool function” in ingenuity pathway analysis (IPA). The top 3 most interconnected molecules and drugs (i.e., the hubs) within the generated networks were considered important targets for the treatment of SNHL.

Results: A total of 70 drugs were investigated with IPA. The metabolomic analysis revealed 2 statistically significant networks (Networks 1 and 2). A network analysis using the “grow-tool function” generated one statistically significant network (Network 3). Hubs of these networks were as follows: P38 mitogen-activated protein kinases (P38 MAPK), p42/p44 MAP kinase (ERK1/2) and glutathione for Network 1; protein kinase B (Akt), nuclear factor kappa B (NFkB) and ERK for Network 2; and dexamethasone, tretinoin, and cyclosporin A for Network 3.

Conclusion: Metabolomic and network analysis of the existing pharmacotherapies for SNHL has pointed to and prioritized a number of potential novel targets for treatment of SNHL.

Copyright © 2014 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company

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