Project description:Atopic dermatitis (AD) is the most common inflammatory skin disease, with high unmet need for new therapies that are safe for chronic use. Emerging data suggest that TH2-cytokines play important roles in a variety of allergic and atopic conditions, including asthma and AD. In early phase clinical trials, dupilumab (a fully human monoclonal antibody against IL-4R? that potently blocks IL-4 and IL-13 signaling) rapidly and markedly improved clinical measures in adults with either asthma (with elevated eosinophil counts) or moderate-to-severe AD. The pathomechanisms that may be impacted by IL-4/13 blockade in these disease settings have not yet been characterized in detail. Transcriptome analyses in pre- and post-treatment skin biopsies from patients with moderate-to-severe AD treated with dupilumab or placebo in two completed clinical trials 18 Patients with AD treated with dupilumab or placebo. 28 biopsies in lesional (LS) Skin (16 pre-treatment and 12 post-treatment). 12 biopsies in non-lesional (NL) Skin (7 pre-treatment and 5 post treatment)
Project description:A phase 2, double-blind, placebo-controlled trial evaluated apremilast efficacy, safety, and pharmacodynamics in adults with moderate to severe atopic dermatitis (AD).
Project description:Atopic dermatitis (AD) is the most common inflammatory skin disease, with high unmet need for new therapies that are safe for chronic use. Emerging data suggest that TH2-cytokines play important roles in a variety of allergic and atopic conditions, including asthma and AD. In early phase clinical trials, dupilumab (a fully human monoclonal antibody against IL-4Rα that potently blocks IL-4 and IL-13 signaling) rapidly and markedly improved clinical measures in adults with either asthma (with elevated eosinophil counts) or moderate-to-severe AD. The pathomechanisms that may be impacted by IL-4/13 blockade in these disease settings have not yet been characterized in detail. Transcriptome analyses in pre- and post-treatment skin biopsies from patients with moderate-to-severe AD treated with dupilumab or placebo in two completed clinical trials
Project description:We conducted a randomized, double-blind, placebo-controlled trial in adults with moderate-to-severe AD unresponsive to conventional topical or systemic treatment. Fezakinumab (ILV-094; anti IL-22 monoclonal antibody) monotherapy was administered for 12 weeks (primary endpoint), and clinical responses were followed until week 20. AD transcriptome significantly improved at week 12 in fezakinumab vs. placebo (p<1E-18).
Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
Project description:This phase 1b, single-center, double-blind study evaluated safety, efficacy, and effect on molecular profiles of a topical Janus kinase/spleen tyrosine kinase (JAK/Syk) inhibitor, cerdulatinib gel 0.37%, in ten adults with mild-to-moderate atopic dermatitis (AD).
Project description:Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). The mechanism of action (MOA) of crisaborole and its effects on lesional measures of disease severity are not yet well-defined. This phase 2a, single-center, vehicle-controlled, intrapatient study was designed to further characterize the MOA of crisaborole through evaluation of clinical efficacy and changes in skin biomarkers in adults (N = 40) with mild-to-moderate AD.
Project description:The effect of anti-mouse IL-4 and/or anti-mouse IL-13 Kinoid vaccines was assessed in a model of atopic dermatitis. Mice were immunized with IL-4 and/or IL13 Kinoids (or the carrier protein CRM197 alone as control). Atopic dermatitis-like pathology was induced by repeated epicutaneous exposures to house dust mite and the enterotoxin B from Staphylococcus aureus (SEB). Lesional skin biopsies were collected for bulk RNA sequencing analysis.
Project description:Atopic dermatitis (AD) is the chronic inflammatory skin disease accompanied with severe pruritus. To explore the roles of EGR1 in atopic dermatitis and the relationship between EGR1 and pruritus-scratching behavior, we used a atopic dermatitis-like mouse model driven by house dust mite (HDM) treatment in wild type and EGR1 KO mice, followed with RNA-sequencing analysis.