Psoriasis and gene therapy

Psoriasis is accepted as a chronic, inflammatory, immune-mediated skin disease triggered by complex environmental and genetic factors. For a long time, disease recurrence, drug rejection, and high treatment costs have remained enormous challenges and burdens to patients and clinicians. Natural products with effective immunomodulatory and anti-inflammatory activities from medicinal plants have the potential to combat psoriasis and complications. Herein, an imiquimod (IMQ)-induced psoriasis-like dermatitis model is established in mice...

Topical ROCEN (Roc), liposomal arthrocen hydrogel, is a robust anti-inflammatory formulation which has been developed for skin diseases such as eczema. Therefore, we aimed to evaluate the efficacy of Roc 2% on the healing of imiquimod (Imiq)-induced psoriasis in a mouse model. Psoriasis was induced by applying Imiq topically to the mice's back skin once daily for five consecutive days. Moreover, a group of animal experiments was treated with Cyclosporine A (CsA), as a standard drug, for comparison with Roc treated group...

PURPOSE: Guselkumab is a highly effective biologic agent for treating psoriasis. This study aimed to explore potential transcription factors involved in psoriasis pathogenesis and response to guselkumab treatment, aiming to provide new therapeutic strategies for psoriasis. PATIENTS AND METHODS: We analyzed gene expression and single-cell RNA-seq data from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) that upregulated in psoriasis and downregulated after guselkumab treatment were subjected to enrichment analyses...

INTRODUCTION: Receptor-interacting protein kinase 1 (RIPK1), a key mediator of inflammation through necroptosis and proinflammatory cytokine production, may play a role in the pathogenesis of immune-mediated inflammatory diseases such as chronic plaque psoriasis. An experimental medicine study of RIPK1 inhibition with GSK2982772 immediate-release formulation at doses up to 60 mg three times daily in mild to moderate plaque psoriasis indicated that efficacy may be improved with higher trough concentrations of GSK2982772...

Biologic therapies targeting the IL-23/IL-17 axis have transformed the treatment of psoriasis. However, the early mechanisms of action of these drugs remain poorly understood. Here, we perform longitudinal single-cell RNA-sequencing in affected individuals receiving IL-23 inhibitor therapy. By profiling skin at baseline, day 3 and day 14 of treatment, we demonstrate that IL-23 blockade causes marked gene expression shifts, with fibroblast and myeloid populations displaying the most extensive changes at day 3...

Biological therapies are safer and more effective against psoriasis than conventional treatments. Even so, 30-50% of psoriatic patients show an inadequate response, which is associated with individual genetic heterogeneity. Pharmacogenetic studies have identified several single nucleotide polymorphisms (SNPs) as possible predictive and prognostic biomarkers for psoriasis treatment response. The objective of this study was to determine the link between several SNPs and the clinical response to biological therapies in patients with moderate-severe psoriasis...

Generalized pustular psoriasis (GPP) is a rare, immune-mediated inflammatory disease with characteristic cutaneous and systemic manifestations. Mutations in the interleukin-36 receptor antagonist (IL36RN) gene have been implicated in its pathogenesis. Spesolimab is a novel systemic biologic therapy that selectively inhibits interleukin-36. It was recently approved by Health Canada and the US FDA for the treatment of GPP flares in adults. Results from phase 1 and 2 studies have been promising. Herein, we review the efficacy and safety of spesolimab for the treatment of GPP flares, as demonstrated in clinical trials...

OBJECTIVE: Psoriasis is a chronic skin disorder caused by abnormal interactions between epidermal and immune cells. Thus, the interplay between the proliferation and differentiation of epidermal components should be tightly regulated to protect against psoriasis. The differentiation process is primarily controlled by transglutaminases (TGs). However, studies on TG enzymes and their molecular alterations in psoriatic skin lesions are limited. Therefore, this study aimed to investigate TG activity and gene and protein expression in human psoriatic and normal skin tissues...

Actinic keratosis (AK) is a common precancerous skin lesion that can develop into cutaneous squamous cell carcinoma (CSCC). AK is characterized by atypical keratinocytes in the skin's outer layer and is commonly found in sun-exposed areas. Like many precancerous lesions, the development of AK is closely associated with genetic mutations. The molecular biology and transcriptional mechanisms underlying AK development are not well understood. Ultraviolet (UV) light exposure, especially UVA and UVB radiation, is a significant risk factor for AK, causing DNA damage and mutagenic effects...

Objective Hydroxychloroquine (HCQ) is a US Food and Drug Administration (FDA)-approved treatment for systemic lupus erythematosus (SLE) through inhibition of antigen presentation and subsequent reduction in T cell activation. Psoriasis relapse after antimalarial therapy have been reported in up to 18% of patients with psoriasis. Here, we explored the role of HCQ on exacerbating dermatitis utilizing an imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model. Methods Thirty-six C57BL/6 female mice were divided into six groups: wild-type control, IMQ-Only, pre-treat HCQ (30 mg/kg and 60 mg/kg HCQ), and co-treat HCQ with IMQ (30 mg/kg and 60 mg/kg HCQ)...

INTRODUCTION: The interleukin-12/23 (IL-12/23) signalling pathway plays an important role in the pathogenesis of psoriasis. In addition, even molecularly targeted therapy has been reported to lose adequate response to treatment. AIM: To determine the expression patterns of mRNAs and miRNAs related to IL-12/23 signalling pathways in the human keratinocyte culture exposed to liposaccharide A (LPS) and then adalimumab in comparison with untreated cells. MATERIAL AND METHODS: Human, adult, low-Calcium, high-Temperature keratinocyte (HaCaT) cultures were exposed to 1 µg/ml LPS for 8 h, and then adalimumab was added to the cultures at a concentration of 8 µg/ml and incubated for 2, 8, and 24 h...

RATIONALE: Acute generalized exanthematous pustulosis (AGEP) is a serious adverse skin reaction characterized by the rapid appearance of densely distributed, small, sterile pustules with erythema. However, its pathogenesis is not fully understood. Hydroxychloroquine is widely used for the treatment of autoimmune diseases. Some patients presenting with AGEP have IL36RN and CARD14 gene mutations. Our report describes a patient with rheumatoid arthritis and AGEP associated with hydroxychloroquine and a newly discovered CARD14 gene mutation...

Psoriasis and chronic ulcers not only significantly impair quality of life but also pose a challenge in dermatological treatment. This study aimed to identify new therapeutic targets and biomarkers for psoriasis and chronic ulcers by comparing their gene expression profiles. The gene expression profiles of psoriatic, wound and chronic ulcer patients, as well as healthy controls, were determined via RNA extraction and next-generation sequencing of biopsies. In order to identify biomarkers, functional enrichment, differential expression analysis and machine learning algorithms were implemented...

BACKGROUND: CT-P43 is a candidate ustekinumab biosimilar in clinical development. OBJECTIVES: This paper aims to demonstrate equivalent efficacy of CT-P43 to originator ustekinumab in adults with moderate to severe plaque psoriasis. METHODS: This double-blind, phase III trial randomised patients (1:1) to receive subcutaneous CT-P43 or originator ustekinumab (45/90 mg for patients with baseline body weight ≤ 100 kg/> 100 kg) at week 0 and week 4 in Treatment Period I...

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with synovial proliferation and bone erosion, which leads to the structural and functional impairment of the joints. Immune cells, together with synoviocytes, induce a pro-inflammatory environment and novel treatment agents target inflammatory cytokines. Psoriasis is a chronic immune-mediated skin disease, and several cytokines are considered as typical mediators in the progression of the disease, including IL-23, IL-22, and IL-17, among others...

Topical medications represent the most commonly used drugs in the treatment of psoriasis. However, topical steroids are mainly limited to short-term or intermittent use, and traditional non-steroidal topicals such as vitamin D analogues, topical calcineurin inhibitors, and topical retinoids are limited by low efficacy and poor local skin tolerability. Tapinarof (GSK2894512, DMVT-505) is a novel, topical aryl hydrocarbon receptor (AHR) agonist, which was recently approved by the FDA for the treatment of plaque psoriasis in adults...

Psoriasis is a common inflammatory disease of especially high recurrence rate (90%) which is suffered by approximately 3% of the world population. The overexpression of reactive oxygen species (ROS) plays a critical role in psoriasis progress. Here we show that biomimetic iron single-atom catalysts (FeN4 O2 -SACs) with broad-spectrum ROS scavenging capability can be used for psoriasis treatment and relapse prevention via related gene restoration. FeN4 O2 -SACs demonstrate attractive multiple enzyme-mimicking activities based on atomically dispersed Fe active structures, which are analogous to those of natural antioxidant enzymes, iron superoxide dismutase, human erythrocyte catalase, and ascorbate peroxidase...

BACKGROUND: Scalp psoriasis seriously affects the appearance and psychological status of patients. The aim of this study was to investigate the effect and potential mechanism of RPL9 and TIFA in scalp psoriasis, so as to provide a precise and effective way for the clinical treatment of scalp psoriasis. METHODS: The Gene Expression Omnibus (GEO) database was employed to download the GSE75343 dataset to search for differentially expressed genes (DEGs) in scalp psoriasis through Sangerbox...

INTRODUCTION: Pruritus is a prevalent symptom, described as one of the most bothersome of psoriasis. Specific itch management remains a challenge, for which hydrotherapy could be used as adjunct care to medical treatment. Therefore, we assessed the immediate and longer-term benefit of 3 weeks of Avène thermal spring water hydrotherapy on chronic pruritus in patients in addition to their usual psoriasis and/or pruritus management. METHODS: Twenty-six patients suffering from chronic pruritus due to psoriasis were evaluated before and after 3 weeks of hydrotherapy with a 3 and 6 month follow-up...

Skin is the first barrier against external threats, and skin immune dysfunction leads to multiple diseases. Psoriasis is an inflammatory, chronic, common, immune-related skin disease that affects more than 125 million people worldwide. RNA interference (RNAi) therapy is superior to traditional therapies, but rapid degradation and poor cell uptake are the greatest obstacles to its clinical transformation. The transdermal delivery of siRNA and controllable assembly/disassembly of nanodrug delivery systems can maximize the therapeutic effect...