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Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease

Corticosteroids, oral or transtympanic, remain the mainstay for inner ear diseases characterized by hearing fluctuation or sudden changes in hearing, including sudden sensorineural hearing loss (SSNHL), Meniere’s disease (MD), and autoimmune inner ear disease (AIED). Despite their use across these d...

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Detalles Bibliográficos
Autores principales: Missner, Alexander A., Johns, James Dixon, Gu, Shoujun, Hoa, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687275/
https://www.ncbi.nlm.nih.gov/pubmed/36358991
http://dx.doi.org/10.3390/biom12111641
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author Missner, Alexander A.
Johns, James Dixon
Gu, Shoujun
Hoa, Michael
author_facet Missner, Alexander A.
Johns, James Dixon
Gu, Shoujun
Hoa, Michael
author_sort Missner, Alexander A.
collection PubMed
description Corticosteroids, oral or transtympanic, remain the mainstay for inner ear diseases characterized by hearing fluctuation or sudden changes in hearing, including sudden sensorineural hearing loss (SSNHL), Meniere’s disease (MD), and autoimmune inner ear disease (AIED). Despite their use across these diseases, the rate of complete recovery remains low, and results across the literature demonstrates significant heterogeneity with respect to the effect of corticosteroids, suggesting a need to identify more efficacious treatment options. Previously, our group has cross-referenced steroid-responsive genes in the cochlea with published single-cell and single-nucleus transcriptome datasets to demonstrate that steroid-responsive differentially regulated genes are expressed in spiral ganglion neurons (SGN) and stria vascularis (SV) cell types. These differentially regulated genes represent potential druggable gene targets. We utilized multiple gene target databases (DrugBank, Pharos, and LINCS) to identify orally administered, FDA approved medications that potentially target these genes. We identified 42 candidate drugs that have been shown to interact with these genes, with an emphasis on safety profile, and tolerability. This study utilizes multiple databases to identify drugs that can target a number of druggable genes in otologic disorders that are commonly treated with steroids, providing a basis for establishing novel repurposing treatment trials.
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spelling pubmed-96872752022-11-25 Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease Missner, Alexander A. Johns, James Dixon Gu, Shoujun Hoa, Michael Biomolecules Article Corticosteroids, oral or transtympanic, remain the mainstay for inner ear diseases characterized by hearing fluctuation or sudden changes in hearing, including sudden sensorineural hearing loss (SSNHL), Meniere’s disease (MD), and autoimmune inner ear disease (AIED). Despite their use across these diseases, the rate of complete recovery remains low, and results across the literature demonstrates significant heterogeneity with respect to the effect of corticosteroids, suggesting a need to identify more efficacious treatment options. Previously, our group has cross-referenced steroid-responsive genes in the cochlea with published single-cell and single-nucleus transcriptome datasets to demonstrate that steroid-responsive differentially regulated genes are expressed in spiral ganglion neurons (SGN) and stria vascularis (SV) cell types. These differentially regulated genes represent potential druggable gene targets. We utilized multiple gene target databases (DrugBank, Pharos, and LINCS) to identify orally administered, FDA approved medications that potentially target these genes. We identified 42 candidate drugs that have been shown to interact with these genes, with an emphasis on safety profile, and tolerability. This study utilizes multiple databases to identify drugs that can target a number of druggable genes in otologic disorders that are commonly treated with steroids, providing a basis for establishing novel repurposing treatment trials. MDPI 2022-11-05 /pmc/articles/PMC9687275/ /pubmed/36358991 http://dx.doi.org/10.3390/biom12111641 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Missner, Alexander A.
Johns, James Dixon
Gu, Shoujun
Hoa, Michael
Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease
title Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease
title_full Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease
title_fullStr Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease
title_full_unstemmed Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease
title_short Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease
title_sort repurposable drugs that interact with steroid responsive gene targets for inner ear disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687275/
https://www.ncbi.nlm.nih.gov/pubmed/36358991
http://dx.doi.org/10.3390/biom12111641
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