Title |
Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis A randomized controlled trial
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Published in |
Annals of Allergy, Asthma & Immunology, March 2018
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DOI | 10.1016/j.anai.2018.03.013 |
Pubmed ID | |
Authors |
Tali Czarnowicki, Anders B Dohlman, Kunal Malik, Diane Antonini, Robert Bissonnette, Tom C Chan, Lisa Zhou, Huei-Chi Wen, Yeriel Estrada, Hui Xu, Catherine Bryson, Jie Shen, Deepak Lala, Avi Ma'ayan, Gerard McGeehan, Richard Gregg, Emma Guttman-Yassky |
Abstract |
Liver X receptors (LXRs) are involved in maintaining epidermal barrier and suppressing inflammatory responses in model systems. The LXR agonist VTP-38543 showed promising results in improving barrier function and inflammatory responses in model systems. To assess the safety, tolerability, cellular and molecular changes, and clinical efficacy of the topical VTP-38543 in adults with mild to moderate atopic dermatitis (AD). A total of 104 ambulatory patients with mild to moderate AD were enrolled in this randomized, double-blind, vehicle-controlled trial between December 2015 and September 2016. VTP-38543 cream in 3 concentrations (0.05%, 0.15%, and 1.0%) or placebo was applied twice daily for 28 days. Pretreatment and posttreatment skin biopsy specimens were obtained from a subset of 33 patients. Changes in SCORing of Atopic Dermatitis, Eczema Area and Severity Index, Investigator's Global Assessment, and tissue biomarkers (by real-time polymerase chain reaction and immunostaining) were evaluated. Topical VTP-38543 was safe and well tolerated. VTP-38543 significantly increased messenger RNA (mRNA) expression of epidermal barrier differentiation (loricrin and filaggrin, P = .02) and lipid (adenosine triphosphate-binding cassette subfamily G member 1 and sterol regulatory element binding protein 1c, P < .01) measures and reduced epidermal hyperplasia markers (thickness, keratin 16 mRNA). VTP-38543 nonsignificantly suppressed cellular infiltrates and down-regulated mRNA expression of several TH17/TH22-related (phosphatidylinositol 3, S100 calcium-binding protein A12) and innate immunity (interleukin 6) markers. Topical VTP-38543 is safe and well tolerated. Its application led to improvement in barrier differentiation and lipids. Longer-term studies are needed to clarify whether a barrier-based approach can induce meaningful suppression of immune abnormalities. clinicaltrials.gov Identifier: NCT02655679. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 33% |
Unknown | 2 | 67% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 33% |
Science communicators (journalists, bloggers, editors) | 1 | 33% |
Scientists | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 52 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 8 | 15% |
Student > Master | 5 | 10% |
Other | 3 | 6% |
Student > Ph. D. Student | 3 | 6% |
Student > Doctoral Student | 3 | 6% |
Other | 8 | 15% |
Unknown | 22 | 42% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 10 | 19% |
Biochemistry, Genetics and Molecular Biology | 3 | 6% |
Immunology and Microbiology | 3 | 6% |
Chemistry | 2 | 4% |
Nursing and Health Professions | 2 | 4% |
Other | 7 | 13% |
Unknown | 25 | 48% |