Metabolomic and Network Analysis of Pharmacotherapies for Sensorineural Hearing Loss

Tjeerd Muurling, Konstantina M. Stankovic
2014 Otology and Neurotology  
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
more » ... 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 "growtool 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. Key Words: ERK1/2VIngenuity pathway analysisVMetabolomic analysisVNetwork medicineVSensorineural hearing lossVTretinoin.
doi:10.1097/mao.0000000000000254 pmid:24335929 fatcat:fsdg63moavcn5aakcs7v7c2di4