Drug Repurposing for Atopic Dermatitis by Integration of Gene Networking and Genomic Information

Atopic Dermatitis (AD) is a chronic and relapsing skin disease. The medications for treating AD are still limited, most of them are topical corticosteroid creams or antibiotics. The current study attempted to discover potential AD treatments by integrating a gene network and genomic analytic approaches. Herein, the Single Nucleotide Polymorphism (SNPs) associated with AD were extracted from the GWAS catalog. We identified 70 AD-associated loci, and then 94 AD risk genes were found by extending to proximal SNPs based on r2> 0.8 in Asian populations using HaploReg v4.1. Next, we prioritized the AD risk genes using in silico pipelines of bioinformatic analysis based on six functional annotations to identify biological AD risk genes. Finally, we expanded them according to the molecular interactions using the STRING database to find the drug target genes. Our analysis showed 27 biological AD risk genes, and they were mapped to 76 drug target genes. According to DrugBank and Therapeutic Target Database, 25 drug target genes overlapping with 53 drugs were identified. Importantly, dupilumab, which is approved for AD, was successfully identified in this bioinformatic analysis. Furthermore, ten drugs were found to be potentially useful for AD with clinical or preclinical evidence. In particular, we identified filgotinub and fedratinib, targeting gene JAK1, as potential drugs for AD. Furthermore, four monoclonal antibody drugs (lebrikizumab, tralokinumab, tocilizumab, and canakinumab...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Acta Derm Venereol. 2021 Oct 7. doi: 10.2340/actadv.v101.307. Online ahead of print.ABSTRACTOptimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a real-world setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo-controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroid in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo...
Source: Acta Derm Venereol A... - Category: Dermatology Authors: Source Type: research
Am J Manag Care. 2021 Oct;27(17 Suppl):S311-S318. doi: 10.37765/ajmc.2021.88756.ABSTRACTEosinophilic esophagitis (EoE) is a chronic inflammatory disease driven by a type 2 immune response and characterized by the accumulation of immune cells (eosinophils, basophils, and mast cells) in the esophagus. Patients may present with EoE at any age, and its prevalence is similar across age groups in the United States. If EoE is suspected, an endoscopy with biopsy is required to confirm the diagnosis; endoscopy allows clinicians to evaluate for the presence of rings, furrows, exudates, edemas, and/or strictures and biopsy helps to i...
Source: The American Journal of Managed Care - Category: Health Management Authors: Source Type: research
AbstractIntroductionSkin pain (described as discomfort or soreness) is increasingly recognized as a symptom of atopic dermatitis which impacts patient quality of life. This analysis examined the effect of baricitinib on skin pain in atopic dermatitis in three phase  3 studies (BREEZE-AD1, -AD2, and -AD7).MethodsPatients were randomly assigned 2:1:1:1 to receive once-daily placebo, baricitinib 1  mg, 2 mg, or 4 mg in BREEZE-AD1 (N = 624) and -AD2 (N = 615) and 1:1:1 to receive once-daily placebo, baricitinib 2 mg, or 4 mg, with topical corticosteroids, in BREEZE-AD7 ...
Source: Dermatology and Therapy - Category: Dermatology Source Type: research
Tissue-resident memory T (Trm) cells are detrimental in numerous chronic inflammatory diseases, including allergic contact dermatitis (ACD), in which they re-instigate and augment the immunopathology. We assessed the impact of a standard corticosteroid treatment, topical triamcinolone acetonide, on the formation, maintenance and reactivation of skin Trm cells in ACD. We used an experimental model of ACD, i.e. contact hypersensitivity (CHS), to 2,4-dinitrofluorobenzene that is mediated by allergen-specific CD8+ T cells.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Source Type: research
Conclusions Clinical research is needed to better determine the diagnostic criteria and to assess the efficacy of treatment options for PCV.
Source: Journal of Lower Genital Tract Disease - Category: OBGYN Tags: Non-HPV Associated Vulvovaginal Topics Source Type: research
Dermatitis. 2021 Sep 27. doi: 10.1097/DER.0000000000000792. Online ahead of print.ABSTRACTBACKGROUND: Although bullous pemphigoid (BP), atopic dermatitis (AD), and allergic rhinitis (AR) are associated with shared pathogenic mechanisms the epidemiological relationship between these conditions remains to be investigated.OBJECTIVE: To evaluate the bidirectional association of BP with AD and AR.METHODS: A population-based retrospective cohort study was performed comparing BP patients (n = 3924) with age-, sex-, and ethnicity-matched control subjects (n = 19,280), with respect to incident cases of AD and AR. A case-control des...
Source: Dermatitis - Category: Dermatology Authors: Source Type: research
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