- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: Involucrin modulates vitamin D receptor activity in the epidermis. (Pubmed Central) - Jan 16, 2023
Coinciding with the dampened MC903-mediated inflammation, skin microbiota of Ivl -/- mice was more stable compared to WT mice, which exhibited a MC903-responsive increase in Bacteroidetes and decrease in Firmicutes. Together, our studies in Ivl -/- mice identify a functional role for Involucrin to positively impact Vdr activity and suggest an emerging IVL/VDR paradigm for adaptation in the human epidermis.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: Topical Skullcapflavone II attenuates atopic dermatitis in a mouse model by directly inhibiting associated cytokines in different cell types. (Pubmed Central) - Jan 7, 2023
We aimed to validate SFII for atopic dermatitis (AD) therapy by demonstrating the anti-inflammatory effects of SFII in an AD mouse model produced by the topical application of the vitamin D3 analog MC903...Lastly, we demonstrated that topical SFII more effectively suppressed serum IgE levels, the production of IL-4 and thymic stromal lymphopoietin (TSLP), and infiltration of CD4 T cells and Gr-1 cells (neutrophils) into lesion skin compared to topical baicalein (a flavonoid derived from Scutellaria baicalensis), which has anti-inflammatory effects. Taken together, our findings suggest that SFII may have promising therapeutic potential for this complex disease via the regulation of multiple AD-associated targets.
- |||||||||| Dupixent (dupilumab) / Sanofi, Regeneron, Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: IL-4Rα signalling in B cells and T cells play differential roles in acute and chronic atopic dermatitis. (Pubmed Central) - Jan 5, 2023
Targeting interleukin 4 receptor alpha (IL-4Rα), an IL-4/IL-13 signalling axis, with dupilumab shows efficacy in AD...We used House dust mite (HDM) and Ovalbumin (OVA) in chronic models and a low-calcemic analog of vitamin D (MC903) for acute models of AD...IL-4Rα-responsive T cells were essential in epidermal thickening in the pan-T cell, but not CD4 or CD8 T cells suggesting the importance of γδT cells during acute AD. Our results suggest that IL-4Rα responsiveness on innate T cells regulates acute atopic dermatitis, while on B cells it regulates IgE.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: A role for age-associated alterations in esophageal epithelium in eosinophilic esophagitis-associated fibrosis. (Pubmed Central) - Jan 3, 2023
We find that induction of EoE inflammation in young and aged mice using the MC903/Ovalbumin protocol for the same time period results in increased lamina propria thickness uniquely in aged animals...Finally, to identify potential mechanisms through which aged esophageal epithelial cells may stimulate fibrotic remodeling, we perform cytokine array experiments in young and aged mice. These studies are significant as identification of age-associated factors that contribute to fibrotic remodeling may aid in the design of strategies toward early detection, prevention, and therapy of fibrostenotic EoE.
- |||||||||| Zyclara (imiquimod) / Mochida, Viatris, Bausch Health, Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: CD1a promotes systemic manifestations of skin inflammation. (Pubmed Central) - Dec 9, 2022
Similar systemic escalation is shown in MC903-induced skin inflammation...The beneficial effect is epitope dependent, and we further characterise the five best-performing antibodies for their capacity to modulate CD1a-expressing cells and ameliorate CD1a-dependent systemic inflammatory responses. In summary, we show that a therapeutically targetable CD1a-dependent pathway may play a role in the systemic spread of cutaneous inflammation.
- |||||||||| AMTX-100 / Amytrx Therap, Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: Genomic control of inflammation in experimental atopic dermatitis. (Pubmed Central) - Nov 9, 2022
P1/2
Consequently, NTCI suppressed skin infiltration by inflammatory cells (eosinophils, macrophages, and CD4 + T lymphocytes), and reduced MC903-evoked proliferation of Ki-67-positive cells. Thus, we highlight the mechanism of action and the potential utility of topical NTCI for treatment of AD undergoing Phase 1/2 clinical trial (AMTX-100 CF, NCT04313400).
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: A population of dermal Langerin dendritic cells promote the inflammation in mouse model of atopic dermatitis. (Pubmed Central) - Nov 4, 2022
This study aimed to investigate the contributions of Langerhans cells (LCs), resident dermal Langerin DCs (r-Langerin dDCs), and newly infiltrated inflammatory dermal Langerin DCs (i-Langerin dDCs) in an AD mouse model induced by the topical application of MC903...Furthermore, TSLP contributed to the upregulation of Langerin expression in BM-derived DCs and promoted the maturation of Langerin DCs. In summary, the present study demonstrated that the newly infiltrated inflammatory dermal Langerin DCs were essential for AD development and local TSLP production, and TSLP further promoted the production of BM-derived i-Langerin dDCs, which might maintain AD inflammation.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
INTERLEUKIN-20 PROMOTES NEURO- INFLAMMATION AND PRURITUS IN ATOPIC DERMATITIS () - Oct 30, 2022 - Abstract #ISAD2022ISAD_148;
Topical MC903 treatment in mice ear enhanced IL-20R1 expression in trigeminal sensory ganglia, suggesting an epidermal-driven mechanism for sensitization of sensory IL-20 signaling...In a Mouse model of acute itch, intradermal injection IL-20 and IL-13 elicited significant itch-like behavior, though only when co-injected. Our findings highlight a role of IL-20 signaling in the pathophysiology of AD, thus forming a new basis for the development of a novel antipruritic strategy via interrupting IL-20 epidermal pathways.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: γδ T cell-mediated Wound Healing is Diminished by Allergic Skin Inflammation. (Pubmed Central) - Sep 29, 2022
A similar loss of DETCs was observed in mice treated topically with MC903...Importantly, intradermal injection of the DETC-produced cytokine FGF7 rescued the rate of wound closure in mice with allergic skin inflammation. Together, these results suggest that the atopic environment diminishes pro-healing T cell populations in the skin that results in attenuated wound healing responses.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: Acupuncture attenuates comorbid anxiety- and depressive-like behaviors of atopic dermatitis through modulating neuroadaptation in the brain reward circuit in mice. (Pubmed Central) - Sep 14, 2022
AD-like skin lesions were induced by the topical application of MC903 to the mouse cheek...The beneficial effects of acupuncture on clinical symptoms (scratching behavior) and comorbid psychological distress in AD strongly correlated with dorsal striatal ΔFosB levels. Collectively, these data indicate that acupuncture had a significant, positive impact on comorbid anxiety- and depression-like behaviors by modulating neuroadaptation in the brain reward circuit in mice with AD, providing a novel perspective for the non-pharmacological management of psychiatric comorbidities of AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: Glycyrrhizic acid suppresses atopic dermatitis-like symptoms by regulating the immune balance. (Pubmed Central) - Sep 14, 2022
Collectively, these data indicate that acupuncture had a significant, positive impact on comorbid anxiety- and depression-like behaviors by modulating neuroadaptation in the brain reward circuit in mice with AD, providing a novel perspective for the non-pharmacological management of psychiatric comorbidities of AD. In conclusion, our findings suggested potential therapeutic effects of GA against MC903-induced AD-like skin lesions in mice.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: A dysregulated sebum-microbial metabolite-IL-33 axis initiates skin inflammation in atopic dermatitis. (Pubmed Central) - Aug 22, 2022
Topical propionate application attenuated skin inflammation in mice with MC903-induced AD-like dermatitis by inhibiting IL-33 production in keratinocytes, an effect that was mediated through inhibition of HDAC and regulation of the AhR signaling pathway...A proof-of-concept clinical study further demonstrated the beneficial therapeutic effects of topical propionate application in AD patients. In summary, we have uncovered that the dysregulated sebum-microbial metabolite-IL-33 axis might play an initiating role in AD-related skin inflammation, thereby highlighting novel therapeutic strategies for the treatment of AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
HY209, a GPCR19 agonist, ameliorates atopic dermatitis in mice (Kiosk #1) - Aug 16, 2022 - Abstract #ESDR2022ESDR_746;
Topical and oral treatment with HY209 ameliorates pro-inflammatory features of AD in mice induced by DNCB and further confirmation using MC903 and oxazolone mice AD models. A keratinocytes-modulator like HY209 might improve clinical symptoms of AD patients synergistically when combined with T cell- modulators.
- |||||||||| Zyclara (imiquimod) / Mochida, Viatris, Bausch Health, GLPG2534 / Galapagos, Dovonex (calcipotriol) / LEO Pharma, Novartis
IRAK4 drives pathogenic processes in inflammatory skin diseases (Kiosk #2) - Aug 16, 2022 - Abstract #ESDR2022ESDR_741;
Here, we profiled a novel, selective IRAK4 inhibitor, GLPG2534, in an extensive series of in vitro, ex vivo, and in vivo models of inflammatory skin diseases (ISD)...Furthermore, disease activity in murine models of psoriasis and atopic dermatitis (AD) skin inflammation (Il-23-, Il-33-, imiquimod- and MC903-induced) was markedly dampened by IRAK4 inhibition...The variety of models highlighted IRAK4 as central mediator of psoriasis and atopic dermatitis by regulating cytokines (e.g. IL-17A, IL-22, IL-23, IL-4, IL-13, IL-5, TNF-α), chemoattractant chemokines (e.g. CXCL8, CXCL5, MCP1) and antimicrobial peptides (e.g. S100A7, DEFB4A). Overall, our data demonstrate the potential of IRAK4 inhibition as a therapeutic strategy in ISD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Ultraviolet radiation-induced antimicrobials neutralize S. aureus and reduce atopic dermatitis-associated inflammation () - Aug 16, 2022 - Abstract #ESDR2022ESDR_492;
To test this hypothesis, we developed a new mouse model of AD by treating the skin with calcipotriol (MC903) and an S. aureus clinical isolate...Taken together, our study demonstrates that UV irradiation can reduce S. aureus associated AD-like inflammation by directly impacting the S. aureus growth and in directly by inducing the expression of AMPs. These results open avenues for the development of new therapeutic strategies using antimicrobials to treat AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
IL-4 Receptor α Blockade Attenuates Allergic Conjunctivitis in a Novel Murine Ocular Model () - Aug 16, 2022 - Abstract #ESDR2022ESDR_246;
Wild-type BALB/c mice were treated epicutaneously with MC903 (calcipotriol)+ ovalbumin (OVA) to evoke AD-like disease and challenged ocularly with OVA or with vehicle control (phosphate-buffered saline [PBS]) once daily for 7 days...In this novel murine model of allergic conjunctivitis, both basophils and CD4+ T cells were necessary for development of conjunctivitis, while IL-4Rα blockade attenuated conjunctivitis development. Anti-IL-4Rα-augmented genes may represent candidate mechanisms for the increased frequency of conjunctivitis in AD patients given treatments targeting IL-4Rα or IL-13.
- |||||||||| Vtama (tapinarof) / Roivant, Japan Tobacco
Journal: Tapinarof cream (Vtama) for psoriasis. (Pubmed Central) - Aug 11, 2022
This study reported for the first time that MHLJDD and its active fraction could be used as innovative therapeutic agents for AD. No abstract available
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
A tough row to hoe: treating a novel recalcitrant facial rash (Lomond / M5) - Jun 23, 2022 - Abstract #BAD2022BAD_89;
She had been initially treated for psoriasis with clobetasone butyrate cream and Dovonex®, and subsequently for actinic keratosis with Efudix® cream without success...New areas continued to occur that responded to mometasone furoate 0·1% ointment...None of the other cases reported in literature describe an association with pregnancy, but in one of our patients the rash started and was subsequently aggravated with pregnancy. The treatment of FDD cannot be generalized and needs to be tailored on a case-by-case basis.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: CD4 T cells play an essential role in chronic MC903-induced skin inflammation. (Pubmed Central) - May 31, 2022
The challenge of MC903 induced skin swelling and type 2 inflammations more rapidly, which was dependent on CD4 T cells and IL-33. We expect that our mouse model will be beneficial for studying the late course of atopic dermatitis.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: The PLAUR signaling promotes chronic pruritus. (Pubmed Central) - May 29, 2022
Serpin E1 inhibitor reduced MC903-induced itch, epidermal hyperplasia, immunocyte infiltration, and resulted in lower transcription/expression levels of Serpin E1 and OSM. Taken together, the PLAUR-TLR2-OSM signaling promotes skin-nerve communication, cutaneous inflammation, and itch, all feeding into an aggravation of AD and exaggerated itch circuits.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: Exposure to Eosinophilic Esophagitis Limits Esophageal Carcinogenesis in a Murine Model. (Pubmed Central) - May 14, 2022
These data indicate that exposure to EoE activates an anti-tumoral immune response that limits esophageal carcinogenesis. These studies have the potential for significant implications related to the clinical care of patients affected by EoE and ESCC.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: IL-20 promotes cutaneous inflammation and peripheral itch sensation in atopic dermatitis. (Pubmed Central) - May 6, 2022
Topical MC903 treatment in mice ear enhanced IL-20R1 expression in the trigeminal sensory ganglia, suggesting a lesion-associated and epidermal-driven mechanism for sensitization of sensory IL-20 signaling...In a murine cheek model of acute itch, intradermal injection IL-20 and IL-13 elicited significant itch-like behavior, though only when co-injected. Our findings provide novel insights into IL-20 function in peripheral (skin-derived) itch and clinically relevant intercellular neuron-epidermal communication, highlighting a role of IL-20 signaling in the pathophysiology of AD, thus forming a new basis for the development of a novel antipruritic strategy via interrupting IL-20 epidermal pathways.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: Convergent total synthesis of (+)-calcipotriol: A scalable, modular approach to vitamin D analogs. (Pubmed Central) - May 5, 2022
This work relates to an improved process for the preparation of intermediates useful for the preparation of a range of VitD derivatives, including calcipotriol, and to processes for preparation of calcipotriol. Strategic bond disconnections enable de novo syntheses of both A- and CD-rings not wedded to semisynthesis.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
EOSINOPHILIC ESOPHAGITIS AND ESOPHAGEAL SQUAMOUS CELL CARCINOMA PROMOTE UNIQUE CELL FATE TRAJECTORIES IN MURINE ESOPHAGEAL EPITHELIUM (27 - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_2336;
Our previous studies pairing MC903/ovalbumin (OVA)-mediated EoE and 4-nitroquinoline 1-oxide (4NQO)-mediated esophageal squamous cell carcinoma (ESCC) in mice indicate that exposure to EoE inflammation inhibits esophageal carcinogenesis...Conclusion s: These data demonstrate that EoE and ESCC have distinct effects on cellular heterogeneity in esophageal epithelium with aberrant basal and superficial populations emerging in the context of cancer and aberrant suprabasal populations emerging in the context of EoE inflammation. Future studies will explore cellular pathways that drive aberrant cell fates in these conditions as well as their functional role in the pathogenesis of EoE and ESCC.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
IL7Rα and TSLPR expression on Langerhans cells in response to inflammatory stimulation (Exhibit Hall; P116) - Apr 8, 2022 - Abstract #IMMUNOLOGY2022IMMUNOLOGY_1059;
Functional assessment of p-STAT5 ex vivo and the dynamic of these receptors in the context of MC903 treatment in vivo is yet to be measured. Our results suggest that tissue resident APC regulate differently cytokines receptors enabling spatial-temporal regulation of proinflammatory signals.
- |||||||||| dexamethasone / Generic mfg.
Journal: CoO Nanozymes with Multiple Catalytic Activities Regulate Atopic Dermatitis. (Pubmed Central) - Feb 27, 2022
The side-effects include skin burns, telangiectasias, and even serious drug dependence. CoO nano-enzymes have a low cytotoxicity and its multiple enzyme-like catalytic activities can effectively protect cells and tissues in ROS environments, which proves that CoO nano-enzymes have high application potential in the field of anti-inflammation.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: CD1dPD-L1CD27 Regulatory Natural Killer Subset Suppresses Atopic Dermatitis. (Pubmed Central) - Feb 24, 2022
Therefore, the objective of this study was to investigate the phenotype and inhibitory functions of transforming growth factor (TGF)-β-producing regulatory NK (NKreg) subset in mice with MC903-induced atopic dermatitis (AD)...Notably, the ratio of splenic Treg per T2 was increased by the adoptive transfer of CD1dPD-L1CD27 NK cells in mice. Taken together, our findings demonstrate that the TGF-β-producing CD1dPD-L1CD27 NK subset has a previously unrecognized role in suppressing T2 immunity and ILC2 activation in AD mice, suggesting that the function of TGF-β-producing NK subset is closely associated with the severity of AD in humans.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Biomarker, Journal: A New Formulation of Probiotics Attenuates Calcipotriol-Induced Dermatitis by Inducing Regulatory Dendritic Cells. (Pubmed Central) - Feb 11, 2022
In this study, we designed a mixture of five strains of probiotics (named IW5) and analyzed the effect and mechanism of IW5 on calcipotriol (MC903)-induced AD-like dermatitis...In cell culture, butyrate induced the production of DCregs. Our study revealed the therapeutic effects of a newly designed probiotics mixture and uncovered a possible mechanism, providing a foundation for future clinical studies.
- |||||||||| Korsuva oral (difelikefalin oral) / Cara Therap, Maruishi Pharma
Oral Difelikefalin Reduces Atopic Dermatitis–Associated Pruritus () - Feb 4, 2022 - Abstract #AAAAI2022AAAAI_1760;
P2
A rapid, significant anti-pruritic effect of DFK was observed in an AD mouse model and in subjects with mild-to-moderate AD. These findings support the role of DFK as an anti-pruritic agent for patients with itch-predominant AD.
- |||||||||| belnacasan (VX-765) / Vertex, Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: A novel function of NLRP3 independent of inflammasome as a key transcription factor of IL-33 in epithelial cells of atopic dermatitis. (Pubmed Central) - Feb 4, 2022
Furthermore, NLRP3 deficient mice exhibited a significant alleviated epidermis inflammation and decreased mRNA expression and secretion of IL-33 in MC903-mediated AD mice without interfering with TSLP and IL-1β production. Our results demonstrate a novel ability of NLRP3 to function as a crucial transcription factor of IL-33 in epithelium independently of inflammasome that to mediate the pathological process of AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: pH and Proton Sensor GPR65 Determine Susceptibility to Atopic Dermatitis. (Pubmed Central) - Jan 5, 2022
Consistent with this genetic association in humans, we show that deficiency of GPR65 in mice resulted in markedly exacerbated disease in the MC903 experimental model of atopic dermatitis...In humans, CD4 T cells from rs8005161 heterozygous individuals expressed higher levels of TNF-α after PMA/ionomycin stimulation, particularly under pH 6 conditions. pH sensing by GPR65 appears to be important for regulating the pathogenesis of atopic dermatitis.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: Atopic dermatitis induces anxiety- and depressive-like behaviors with concomitant neuronal adaptations in brain reward circuits in mice. (Pubmed Central) - Nov 24, 2021
AD-like lesions were induced by the repeated intradermal application of MC903 into the cheek of the mouse...Striatal BDNF, phospho-DARPP32 and phospho-CREB levels were significantly associated with the levels of depressive-like behavior in these mice. Taken together, these findings demonstrate that AD-like skin lesion elicits anxiety- and depressive-like phenotypes that are associated with neuroplasticity-related changes in reward circuitry, providing a better understanding of AD-associated emotional impairments.
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