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Psoriasis and gene therapy

A Batalla, E Coto, J Gómez, N Eirís, D González-Fernández, C Gómez-De Castro, E Daudén, M Llamas-Velasco, R Prieto-Perez, F Abad-Santos, G Carretero, F S García, Y B Godoy, L F Cardo, B Alonso, S Iglesias, P Coto-Segura
Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months...
September 27, 2016: Pharmacogenomics Journal
Tony J Kenna, Aimee Hanson, Mary-Ellen Costello, Matthew A Brown
Ankylosing spondylitis (AS) is a highly heritable disease for which there is a great unmet need for improved therapies. Genetics research has identified several major pathways involved in the disease, from which treatments have either now entered clinical practice or are in development. In particular, therapies targeting the IL-23 pathway were repositioned for use in AS following the discovery of multiple genes in the pathway as determinants of AS risk. Discovery of the association of aminopeptidase genes with AS, and subsequently with psoriasis, inflammatory bowel disease and other conditions, has triggered research into therapies targeting this pathway...
October 2016: Current Rheumatology Reports
Martin Beránek, Zdeněk Fiala, Jan Kremláček, Ctirad Andrýs, Květoslava Hamáková, Vladimír Palička, Lenka Borská
Goeckerman therapy (GT) represents an effective treatment of psoriasis including a combination of pharmaceutical grade crude coal tar (CCT) and ultraviolet irradiation (UV-R). Coal tar contains a mixture of polycyclic aromatic hydrocarbons. The best known carcinogenic polyaromate - benzo[a]pyrene is metabolized into a highly reactive benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE). Glutathione S-transferase M1 (GSTM1) catalyses the conjugation of drugs, toxins and products of oxidative stress with glutathione. The aim of the study is to found possible associations between GSTM1 genotypes and the level of BPDE-DNA adducts in 46 psoriatic patients treated with GT...
August 29, 2016: Acta Medica (Hradec Králové)
Luca Bianchi, Gaetana Costanza, Elena Campione, Manuela Ruzzetti, Alessandro Di Stefani, Laura Diluvio, Emiliano Giardina, Raffaella Cascella, Paola Cordiali-Fei, Claudio Bonifati, Andrea Chiricozzi, Giuseppe Novelli, Fabrizio Ensoli, Augusto Orlandi
BACKGROUND: Clinical or quality of life assessments are currently available for psoriasis severity evaluation and therapeutic response. Laboratory scores focused to measure and follow treatment efficacy are lacking at present. METHODS: Design a microscopic and biomolecular score to monitor skin disease severity and clinical response to anti-psoriatic treatments. A susceptibility gene analysis on cellular retinoic acid binding protein-II (CRABP-II), acting on keratinocyte differentiation, was also performed...
September 14, 2016: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
Monika Białecka, Roksana Ostasz, Mateusz Kurzawski, Adam Klimowicz, Honorata Fabiańczyk, Piotr Bojko, Violetta Dziedziejko, Krzysztof Safranow, Anna Machoy-Mokrzyńska, Marek Droździk
BACKGROUND: Recent studies have revealed the pivotal role of Th17 cells and interleukin-17 (IL-17) in plaque psoriasis development and treatment outcome. The IL-17 family consists of 6 structurally related cytokines (IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, IL-17F), of which IL-17A and IL-17F mediate similar biological effects. OBJECTIVES: The aim of this study was to evaluate an association between the IL17A (-197G>A; rs2275913) and IL17F (rs763780: T>C; rs11465553: G>A; rs2397084: T>C) polymorphisms with psoriasis susceptibility as well as response to topical and combined topical with narrow-band ultraviolet B (NB-UVB) therapy in a Polish population...
September 3, 2016: Dermatology: International Journal for Clinical and Investigative Dermatology
Amy S Paller, Yael Renert-Yuval, Maria Suprun, Hitokazu Esaki, Margeaux Oliva, Thy Nhat Huynh, Benjamin Ungar, Norma Kunjravia, Rivka Friedland, Xiangyu Peng, Xiuzhong Zheng, Yeriel D Estrada, James G Krueger, Keith A Choate, Mayte Suárez-Fariñas, Emma Guttman-Yassky
BACKGROUND: The ichthyoses are rare genetic disorders associated with generalized scaling, erythema, and epidermal barrier impairment. Pathogenesis-based therapy is largely lacking, since the underlying molecular basis is poorly understood. OBJECTIVE: To characterize molecularly cutaneous inflammation and its correlation with clinical and barrier characteristics. METHODS: We analyzed biopsies from 21 genotyped ichthyosis patients (congenital ichthyosiform erythroderma (n=6), lamellar ichthyosis (n=7), epidermolytic ichthyosis, (n=5) and Netherton syndrome (n=3)) by immunohistochemistry and RT-PCR and compared them with healthy controls, and atopic dermatitis (AD) and psoriasis patients...
August 20, 2016: Journal of Allergy and Clinical Immunology
Teresa María Linares-Pineda, Marisa Cañadas-Garre, Antonio Sánchez-Pozo, Miguel Ángel Calleja-Hernández
Psoriasis is a chronic inflammatory autoimmune skin disease, characterized by the formation of erythematous scaly plaques on the skin and joints. The therapies for psoriasis are mainly symptomatic and sometimes with poor response. Response among patients is very variable, especially with biological drugs (adalimumab, etarnecept, infliximab and ustekimumab). This variability may be partly explained by the effect of different genetic backgrounds. This has prompted the investigation of many genes, such as FCGR3A, HLA, IL17F, IL23R, PDE3A-SLCO1C1, TNFα and other associated genes, as potential candidates to predict response to the different biological drugs used for the treatment of psoriasis...
August 12, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Frank Kolbinger, Christian Loesche, Marie-Anne Valentin, Xiaoyu Jiang, Yi Cheng, Philip Jarvis, Thomas Peters, Claudio Calonder, Gerard Bruin, Florine Polus, Birgit Aigner, David M Lee, Manfred Bodenlenz, Frank Sinner, Thomas Rudolf Pieber, Dhavalkumar D Patel
BACKGROUND: IL-17A is a key driver of human autoimmune diseases, particularly psoriasis. OBJECTIVE: We sought to determine the role of IL-17A in psoriasis pathogenesis, and to identify a robust, measurable biomarker of IL-17A-driven pathology. METHODS: We studied 8 healthy and 8 psoriasis subjects before and after administration of secukinumab, a fully human anti-IL-17A mAb, and utilized a combination of classical techniques and a novel skin microperfusion assay to evaluate the expression of 170 proteins in blood, non-lesional skin and lesional skin...
August 5, 2016: Journal of Allergy and Clinical Immunology
A Tsianakas, U Mrowietz
Psoriasis is a common chronic inflammatory disease with an incidence of about 0.5-3 %. Previously psoriasis was not primarily regarded to be associated with pruritus; however, this perception has changed in recent years. Meanwhile data conclusively show that between 64 and 97 % of patients report about pruritus that can be severe in a number of cases. Apart from suffering from psoriasis, the presence of pruritus causes additional stress and leads to a significant impairment of health-related quality of life...
August 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
A Campanati, M Orciani, R Lazzarini, G Ganzetti, V Consales, G Sorgentoni, R Di Primio, A Offidani
Psoriasis is a disease characterized by an imbalance between Th1 -Th17 and Th2 inflammatory axes, in which Cutaneous Mesenchymal Stem Cells (MSCs) are early involved, as they show a greater relative expression of several genes encoding for Th1 and Th17 cytokines. Therapeutic implications of TNF-α inhibitors on differentiated skin cells have been largely described in psoriasis, however their effects on MSCs derived from psoriasis patients have been only partially described. Aim of this work was to evaluate the effect of TNF-α inhibitors on cytokine milieu expressed by MSCs isolated from the skin of psoriasis patients...
July 4, 2016: Experimental Dermatology
Aleksandra Batycka-Baran, Petra Besgen, Ronald Wolf, Jacek C Szepietowski, Joerg C Prinz
Psoriasis is a common, chronic immune-mediated inflammatory disease. The inflammatory process in psoriasis has systemic effects and may influence the development of psoriatic comorbidities. The systemic action of phototherapy in patients with psoriasis has been so far poorly elucidated. We aimed to investigate the expression of genes encoding selected psoriasis-related cytokines in peripheral blood mononuclear cells (PBMCs) isolated from patients with psoriasis before and after treatment with phototherapy. 17 patients with mild to moderate plaque psoriasis were treated with narrow band-UVB (NB-UVB), 8 patients with moderate to severe plaque psoriasis with bath-psoralen-ultraviolet A therapy (PUVA)...
August 2016: Journal of Photochemistry and Photobiology. B, Biology
Saakshi Khattri, Patrick M Brunner, Sandra Garcet, Robert Finney, Steven R Cohen, Margeaux Oliva, Riana Dutt, Judilyn Fuentes-Duculan, Xiuzhong Zheng, Xuan Li, Kathleen M Bonifacio, Norma Kunjravia, Israel Coats, Inna Cueto, Patricia Gilleaudeau, Mary Sullivan-Whalen, Mayte Suárez-Fariñas, James G Krueger, Emma Guttman-Yassky
BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory skin disease, but treatment options for moderate-to-severe disease are limited. Ustekinumab is an IL-12/IL-23p40 antagonist that suppresses Th1, Th17 and Th22 activation, commonly used for psoriasis patients. OBJECTIVE: We sought to assess efficacy and safety of ustekinumab in moderate-to-severe AD patients. METHODS: In this phase II, double-blind, placebo-controlled study, 33 patients with moderate-to-severe AD were randomly assigned to either ustekinumab (n=16) or placebo (n=17), with subsequent crossover at 16wks, and last dose at 32wks...
June 15, 2016: Experimental Dermatology
Alison Sutherland, Rebecca J Power, Proton Rahman, Darren D O'Rielly
INTRODUCTION: Topical, systemic, oral disease modifying, and biologic agents are part of the armamentarium to manage psoriatic disease. The choice of therapy depends upon disease severity, relevant co-morbidities and patient preference. There is great variability in patient response with these agents, and there is still no clear method of selecting the preferred therapeutic agent for efficacy or lack of adverse events. AREAS COVERED: This article will review the pharmacogenetic and pharmacogenomic targets that are currently known with respect to psoriasis vulgaris, and the most frequent co-morbidity of psoriasis, psoriatic arthritis...
August 2016: Expert Opinion on Drug Metabolism & Toxicology
Zhilong Jia, Ying Liu, Naiyang Guan, Xiaochen Bo, Zhigang Luo, Michael R Barnes
BACKGROUND: Drug repositioning, finding new indications for existing drugs, has gained much recent attention as a potentially efficient and economical strategy for accelerating new therapies into the clinic. Although improvement in the sensitivity of computational drug repositioning methods has identified numerous credible repositioning opportunities, few have been progressed. Arguably the "black box" nature of drug action in a new indication is one of the main blocks to progression, highlighting the need for methods that inform on the broader target mechanism in the disease context...
2016: BMC Genomics
Lívia Vieira Depieri, Lívia Neves Borgheti-Cardoso, Patrícia Mazureki Campos, Katia Kaori Otaguiri, Fabiana Testa Moura de Carvalho Vicentini, Luciana Biagini Lopes, Maria José Vieira Fonseca, M Vitória Lopes Badra Bentley
Gene therapy by RNA interference (RNAi) is a post-transcriptional silencing process that can suppress the expression of a particular gene and it is a promising therapeutic approach for the treatment of many severe diseases, including cutaneous disorders. However, difficulties related to administration and body distribution limit the clinical use of small interfering RNA (siRNA) molecules. In this study, we proposed to use nanocarriers to enable siRNA application in the topical treatment of skin disorders. A siRNA nanodispersion based on liquid crystalline phase and composed of monoolein (MO), oleic acid (OA) and polyethylenimine (PEI) was developed and its physicochemical properties, efficiency of complexation and carrier/siRNA stability were assessed...
August 2016: European Journal of Pharmaceutics and Biopharmaceutics
Natalie Garzorz-Stark, Linda Krause, Felix Lauffer, Anne Atenhan, Jenny Thomas, Sebastian P Stark, Regina Franz, Stephan Weidinger, Anna Balato, Nikola S Mueller, Fabian J Theis, Johannes Ring, Carsten B Schmidt-Weber, Tilo Biedermann, Stefanie Eyerich, Kilian Eyerich
Novel specific therapies for psoriasis and eczema have been developed, and they mark a new era in the treatment of these complex inflammatory skin diseases. However, within their broad clinical spectrum, psoriasis and eczema phenotypes overlap making an accurate diagnosis impossible in special cases, not to speak about predicting the clinical outcome of an individual patient. Here, we present a novel robust molecular classifier (MC) consisting of NOS2 and CCL27 gene that diagnosed psoriasis and eczema with a sensitivity and specificity of >95% in a cohort of 129 patients suffering from (i) classical forms; (ii) subtypes; and (iii) clinically and histologically indistinct variants of psoriasis and eczema...
October 2016: Experimental Dermatology
Martin Beranek, Zdenek Fiala, Jan Kremlacek, Ctirad Andrys, Kvetoslava Hamakova, Marcela Chmelarova, Vladimir Palicka, Lenka Borska
Goeckerman therapy (GT) for psoriasis combines the therapeutic effect of crude coal tar (CCT) and ultraviolet radiation (UVR). CCT contains polycyclic aromatic hydrocarbons, some of which can form DNA adducts that may induce mutations and contribute to carcinogenesis. The aim of our work was to evaluate the relationship between concentrations of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA adducts) and rs4646903 (CYP1A1 gene), rs1048943 (CYP1A1), rs1056836 (CYP1B1), rs1051740 (EPHX1), rs2234922 (EPHX1) and rs8175347 (UGT1A1) polymorphic sites, and GSTM1 null polymorphism in 46 patients with chronic stable plaque psoriasis who underwent GT...
July 25, 2016: Toxicology Letters
Maria I Ramos, Marcel B M Teunissen, Boy Helder, Saida Aarrass, Maria J H de Hair, Arno W van Kuijk, Danielle M Gerlag, Paul P Tak, Maria C Lebre
OBJECTIVES: We aimed to investigate the early changes in expression of C-type lectin domain family 9, member A (CLEC9A), a C-type lectin that is specifically expressed by the CD141(+) dendritic cell subset that is involved in cross-presentation to CD8(+) T cells, by evaluating gene and/or protein expression in three different compartments [skin, synovial tissue (ST) and serum] after short-term adalimumab treatment in PsA patients compared with placebo. METHODS: Patients with active PsA and psoriasis were randomized to receive adalimumab or placebo for 4 weeks...
September 2016: Rheumatology
Sebastian Podlipnik, Lorena de la Mora, Mercè Alsina, José M Mascaró
Pneumocystis jirovecii pneumonia (PCP) is a relatively rare complication in non-HIV patients receiving immunosuppressive treatment. Since the introduction of tumour necrosis factor-α inhibitors cases of this complication have increased. We report the case of a 54-year-old, HIV-negative patient, who presented to our department with a long history of pustular psoriasis with poor response to traditional treatments. During the last admission he developed a severe flare that was unresponsive to cyclosporine, therefore infliximab was initiated...
May 12, 2016: Australasian Journal of Dermatology
Y Kimura, R Shimada-Omori, T Takahashi, K Tsuchiyama, Y Kusakari, K Yamasaki, R Nishikawa, C Nishigori, S Aiba
BACKGROUND: TNF-α antagonist therapy (TNF-AT) is currently used for moderate and severe psoriasis. However, this treatment has several drawbacks, e.g., inter-individual variability in clinical response, and secondary loss of effectiveness. OBJECTIVE: To quantitatively evaluate the TNF-α neutralizing activity (TNF-NA) of psoriatic patients' plasma during TNF-AT and to objectively determine poor responders. METHODS: We used a human IL-8 reporter monocyte cell line, THP-G8, that harbors a stable luciferase orange (SLO) gene under the control of the IL-8 promoter...
May 7, 2016: British Journal of Dermatology
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