Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease.
Repurposable Drugs That Interact with Steroid Responsive Gene Targets for Inner Ear Disease.
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DOI：
10.3390/biom12111641
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发表时间：
2022-11-05
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
口服或经鼓膜的皮质类固醇仍然是以听力波动或听力突然变化为特征的内耳疾病的主要药物，包括突发性感音神经性听力损失（SSNHL）、梅尼埃病（MD）和自身免疫性内耳疾病（AIED）。尽管在这些疾病中使用，但完全恢复率仍然很低，并且文献中的结果表明皮质类固醇的作用存在显著异质性，这表明需要确定更有效的治疗方案。以前，我们的小组交叉引用了耳蜗中的类固醇反应基因与已发表的单细胞和单核转录组数据集，以证明类固醇反应差异调节基因在螺旋神经节神经元（SGN）和血管纹（SV）细胞类型中表达。这些差异调节的基因代表了潜在的药物靶基因。我们利用多个基因靶标数据库（DrugBank、Pharos和LINCS）来鉴定口服给药的、FDA批准的潜在靶向这些基因的药物。我们确定了42种已被证明与这些基因相互作用的候选药物，重点是安全性和耐受性。这项研究利用多个数据库来确定药物，这些药物可以靶向通常用类固醇治疗的耳科疾病中的一些可药用基因，为建立新的再利用治疗试验提供基础。
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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影响因子：
14.9
作者：
Nguyen DT;Mathias S;Bologa C;Brunak S;Fernandez N;Gaulton A;Hersey A;Holmes J;Jensen LJ;Karlsson A;Liu G;Ma'ayan A;Mandava G;Mani S;Mehta S;Overington J;Patel J;Rouillard AD;Schürer S;Sheils T;Simeonov A;Sklar LA;Southall N;Ursu O;Vidovic D;Waller A;Yang J;Jadhav A;Oprea TI;Guha R
通讯作者：
Guha R
影响因子：
2.1
作者：
Chandrasekhar, SS
通讯作者：
Chandrasekhar, SS
影响因子：
3.4
作者：
Casani, Augusto Pietro;Piaggi, Paolo;Dallan, Iacopo
通讯作者：
Dallan, Iacopo
影响因子：
2.6
作者：
Cinamon, U;Bendet, E;Kronenberg, J
通讯作者：
Kronenberg, J
影响因子：
4.1
作者：
Advani D;Kumar P
通讯作者：
Kumar P