New therapeutic strategy for atopic dermatitis by targeting CHI3L1/ITGA5 axis.
Ontology highlight
ABSTRACT:
SUBMITTER: Lee YS
PROVIDER: S-EPMC8858621 | biostudies-literature | 2022 Feb
REPOSITORIES: biostudies-literature
Publications
New therapeutic strategy for atopic dermatitis by targeting CHI3L1/ITGA5 axis.
Lee Yong Sun YS Yu Ji Eun JE Kim Min Ji MJ Ham Hyeon Joo HJ Jeon Seong Hee SH Yun Jaesuk J Song Suk-Gil SG Lee Chong-Kil CK Han Sang Bae SB Son Dong Ju DJ Hong Jin Tae JT
Clinical and translational medicine 20220201 2
Similar Datasets
Project description:Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation and skin barrier dysfunction. We are currently experiencing a new era of understanding of the pathogenesis of AD and, as a consequence, a new era of innovation in therapeutics, including small molecules and biologic therapy. Recently, advances in translational research have challenged the traditional AD pathogenesis paradigm of AD being solely a Th2-dominant disease. Other immune pathways seem to play a role in the complex AD pathophysiology, although the clinical relevance of these additional immune pathway abnormalities is unclear. Type 1, type 22, and type 17 pathway activation (with related cytokines/chemokines) have been demonstrated in the skin and blood of AD patients. Type 2 (interleukin [IL]-4, IL-13), IL-31, and type 22 (IL-22) pathway cytokines are increased in AD acute lesions. IL-22 induces both an epidermal hyperplasia at the onset of acute AD and a marked increase in the terminal differentiation S100 genes. This understanding of pathogenesis corresponds to a historic increase in therapeutic development in AD. The extreme clinical heterogeneity and the chronic progression of AD establish the need for newer, safer, and more effective treatments, control the disease, and improve the quality of life of affected patients.
| S-EPMC7875213 | biostudies-literature
Project description:Atopic dermatitis (AD) is a recurrent, chronic, and inflammatory skin disease, which processes with severe itchiness. It often coexists with different atopic diseases. The number of people suffering from AD is relatively high. Epidemiological research demonstrates that 15⁻30% of children and 2⁻10% adults suffer from AD. The disease has significant negative social and economic impacts, substantially decreasing the quality of life of the patients and their families. Thanks to enormous progress in science and technology, it becomes possible to recognise complex genetic, immunological, and environmental factors and epidermal barrier defects that play a role in the pathogenesis of AD. We hope that the new insight on cytokines in AD will lead to new, individualised therapy and will open different therapeutic possibilities. In this article, we will focus on the cytokines, interleukin (IL)-17, IL-19, IL-33, and TSLP (thymic stromal lymphopoietin), which play a significant role in AD pathogenesis and may become the targets for future biologic therapies in AD. It is believed that the new era of biological drugs in AD will give a chance for patients to receive more successful treatment.
| S-EPMC6213458 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation and skin barrier dysfunction. Currently, we are experiencing a new era of understanding of the pathogenesis of AD and, as a consequence, a new era of innovation in therapeutics, including small molecules and biologic therapy. In contrast to biologics, small molecules are similar to conventional pharmacologic chemical agents used as drugs and are generally prepared by chemical synthesis. Unlike biologics, these drugs often are taken orally or formulated for topical use. The purpose of this review is to summarize the efficacy and safety of the current topical and systemic new therapies in AD by reviewing recently published papers on therapies currently in phase 2 or 3 clinical trials. In this review, it is important to note the characteristics of the study population, the primary endpoints, and whether or not there was concomitant topical therapy allowed. These study design elements may significantly alter the results of studies and should be taken into account. Targeted therapy help push AD treatment into a new era of personalized medicine.
| S-EPMC8082001 | biostudies-literature
Project description:Microbiome dysbiosis and cytokine alternations are key features of atopic dermatitis (AD) and psoriasis (PsO), two of the most prevalent and burdensome pruritic skin conditions worldwide. Interleukin (IL)-33 and IL-31 have been recognized to be major players who act synergistically in the pathogenesis and maintenance of different chronic inflammatory conditions and pruritic skin disorders, including AD and PsO, and their potential role as therapeutic targets is being thoroughly investigated. The bidirectional interplay between dysbiosis and immunological changes has been extensively studied, but there is still debate regarding which of these two factors is the actual causative culprit behind the aetiopathological process that ultimately leads to AD and PsO. We conducted a literature review on the Pubmed database assessing articles of immunology, dermatology, microbiology and allergology with the aim to strengthen the hypothesis that dysbiosis is at the origin of the IL-33/IL-31 dysregulation that contributes to the pathogenesis of AD and PsO. Finally, we discussed the therapeutic options currently in development for the treatment of these skin conditions targeting IL-31, IL-33 and/or the microbiome.
| S-EPMC10377073 | biostudies-literature
Project description:Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and significantly impacts patients' lives, particularly in its severe forms. AD clinical presentation varies over the course of the disease, throughout different age groups, and across ethnicities. AD is characterized by a spectrum of clinical phenotypes as well as endotypes. Starting from the current description of AD pathogenesis, this review explores the rationale of approved AD therapies from emollients to biologicals and introduces novel promising drugs.
| S-EPMC8508966 | biostudies-literature
Project description:Recent evidence showed that the postulated linear progression of the atopic march, from atopic dermatitis to food and respiratory allergies, does not capture the heterogeneity of allergic phenotypes, which are influenced by complex interactions between environmental, genetic, and psychosocial factors. Indeed, multiple atopic trajectories are possible in addition to the classic atopic march. Nevertheless, atopic dermatitis is often the first manifestation of an atopic march. Improved understanding of atopic dermatitis pathogenesis is warranted as this could represent a turning point in the prevention of atopic march. In this review, we outline the recent findings on the pathogenetic mechanisms leading to atopic dermatitis that could be targeted by intervention strategies for the prevention of atopic march.
| S-EPMC9029734 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease that is characterized by complex immune dysregulation and skin barrier dysfunction with a wide variety of clinical phenotypes. Until recently, conventional therapeutic modalities for AD remained rather non-specific despite AD's complex etiology. Failing to take into account the underlying inflammatory pathways led to treatments with inadequate efficacy or unacceptable long-term toxicities. We are currently in the midst of a therapeutic renaissance in AD. Recent progress in molecular medicine provides us a better understanding of the AD pathogenesis, suggesting a dominant helper T cell (Th) 2/Th22 response with a varying degree of Th1/Th17 overexpression. Targeted therapeutic agents including biologics and small molecule inhibitors in development hold promises for more effective and safer therapeutic approaches for AD. A better understanding of individual differences amongst AD patients will allow for a more tailored approach in the future. This review aims to cover the most promising emerging therapies in the field of atopic dermatitis utilizing recently published manuscripts and up-to-date conference abstracts and presentations.
| S-EPMC9189747 | biostudies-literature
Project description:Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.
| S-EPMC8137993 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic inflammatory skin condition that can have tremendous impact on quality of life for affected children and adults. First-line therapy for acute management of AD includes topical therapies such as corticosteroids, calcineurin inhibitors, and, more recently, the phosphodiesterase inhibitor crisaborole. Topical agents have remained the mainstay therapy for decades; however, there has been a longstanding need for topical therapies with high efficacy and low risk of adverse effects with long-term use. Given the ongoing advances in understanding the pathogenesis of AD, there are novel targets for pharmacological intervention. We are now in an unprecedented time with more than 40 topical treatments in the pipeline for AD in addition to many developments and treatments on the horizon. This review summarizes selected therapeutic topical agents in later phases of development that target various aspects in the pathogenesis of AD such as Janus kinase inhibition (ruxolitinib and delgocitinib), phosphodiesterase-4 inhibition (roflumilast and difamilast), aryl hydrocarbon modulation (tapinarof), and modulation of the microbiome. We also review novel targeted therapies that are in early phase clinical trials, including AMTX-100, BEN-2293, and PRN473. Preliminary findings on efficacy and tolerability of most of these agents are promising, but further studies are warranted to evaluate the long-term safety and efficacy of these novel agents against the current standard of care.
| S-EPMC9464760 | biostudies-literature
Project description:Atopic Dermatitis (AD) is characterized by skin barrier disruption and an aberrant immune response. Doxycycline is tetracycline antibiotics broadly used systemically to treat inflammatory dermatologic conditions. Several studies have shown doxycycline has anti-inflammatory and pro-healing properties, mainly by blocking tissue proteolytic activity. It is our hypothesis that daily application of a novel doxycycline topical formulation in AD subjects will reduce severity of the disease, by blocking cutaneous proteases activity and restoring skin barrier function and inflammation. To test this hypothesis, we performed a proof of concept, open-label clinical study. Subjects enrolled in the study (n = 15) applied NanoDOX® Hydrogel 1% daily for 4 weeks on a chosen eczematous area. Investigational drug was well tolerated, and no local or systemic adverse events due to investigational drug were reported. Notably, a significant clinical improvement was observed based on a modified Eczema Area & Severity Index (EASI) score of the treated area from start of treatment to 14 and 28 days post-treatment (P < .001). A significant improvement of pruritus was also observed (P = .02). This proof of concept clinical trial is first to explore the impact of a non-systemic doxycycline treatment on AD patients. Our results provide evidence to investigate novel AD treatment strategies targeting cutaneous proteases activity.
| S-EPMC7790433 | biostudies-literature