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. 2022 Nov 5;12(11):1641.
doi: 10.3390/biom12111641.

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

Alexander A Missner  1 , James Dixon Johns  2 , Shoujun Gu  3 , Michael Hoa  2   3
Affiliations

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

Alexander A Missner et al. Biomolecules. .

Abstract

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.

Keywords: Meniere’s disease; RNA sequencing; autoimmune inner ear disease; cochlea; corticosteroids; drug repurposing; spiral ganglion neurons; stria vascularis; sudden sensorineural hearing loss; transcriptome; transtympanic steroids.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
SIDER Side Effect Profile for the antidepressants. These drugs include amitriptyline, doxepin, fluoxetine, fluvoxamine, imipramine, milnacipran, and nefazodone. Frequencies of the top 10 side effects are shown based on the negative logarithm of their respective p values.
Figure 2
Figure 2
SIDER Side Effect Profile on antipsychotics. These drugs include aripiprazole, thioridazine, and loxapine. Frequencies of the top 10 side effects are shown based on the negative logarithm of their respective p values.
Figure 3
Figure 3
SIDER Side Effect Profile of drugs that work in the central nervous system. These drugs include donepezil, gabapentin, memantine, phenytoin, amantadine, and atomoxetine. Frequencies of the top 10 side effects shown are displayed according to the negative logarithm of their respective p values.
Figure 4
Figure 4
SIDER side effect profile on adrenergic modulators. These drugs include carvedilol, doxazosin, prazosin, terazosin, ephedrine, and tizanidine. Frequencies of the top 10 side effects are shown based on the negative logarithm of their respective p values.
Figure 5
Figure 5
SIDER side effect profile on calcium channel blockers. Frequencies of the top 10 side effects shown for nifedipine and verapamil are based on the negative logarithm of their respective p values.
Figure 6
Figure 6
SIDER side effect profile on ion modulators including calcium supplementation and spironolactone. Frequencies of the top 10 side effects shown for the following drugs: calcium citrate, calcium phosphate, and spironolactone based on the negative logarithm of their respective p values.
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