- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: Oral Administration of Taurodeoxycholate, A GPCR19 Agonist, Effectively Ameliorates Atopic Dermatitis in A Mouse Model. (Pubmed Central) - Oct 21, 2024
In this study, we further evaluated the efficacy of orally administered TDCA on MC903- and dinitrochlorobenzene (DNCB)-induced AD mouse models...TDCA also suppressed the expression of thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-13, IL-33, IL-1?, tumour necrosis factor-alpha (TNF-?) and chemokine (C-C motif) ligand 17 in the skin and blood. Given the previously demonstrated safety profiles of TDCA, oral TDCA may offer a beneficial and safer alternative for AD patients.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: Preventive and Therapeutic Effects of Lactiplantibacillus plantarum HD02 and MD159 through Mast Cell Degranulation Inhibition in Mouse Models of Atopic Dermatitis. (Pubmed Central) - Sep 14, 2024
The two strains significantly attenuated vascular permeability induced by mast cell degranulation in a passive cutaneous anaphylaxis (PCA) model and, in the MC903-induced murine atopic dermatitis (AD) model, demonstrated comparable preventive effects against allergies, reducing blood levels of MCPT-1 (mast cell protease-1) and total IgE...Our findings highlight L. plantarum HD02 and MD159 as promising candidates for the prevention and treatment of allergies, demonstrating significant efficacy in suppressing mast cell degranulation, reducing the number of allergy biomarkers, and modulating immune responses in experimental models of AD. Their distinct mechanisms of action suggest potential complementary roles in addressing allergic diseases, underscoring their therapeutic promise in clinical applications.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Epidermal TET2 Regulates the Inflammatory Microenvironment in Atopic Dermatitis (Poster Area) - Aug 5, 2024 - Abstract #EADV2024EADV_2260;
TET2, as an important epigenetic modification molecule, is able to interact with environmental factors to regulate the AD2-type inflammatory response, disruption of epidermal barrier function, and dysbiosis of microflora, which in turn affects the formation of the inflammatory microenvironment of AD. The role of TET2 in the pathogenic mechanism of AD deserves further investigation and has the potential to become a new targeted therapeutic molecule for AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: Effect of a topical traditional Chinese herbal medicine on skin microbiota in mouse model of atopic dermatitis. (Pubmed Central) - Jul 26, 2024
Medication-free matrix ointment, CSZYRG, and mometasone furoate cream (positive control group) were applied to the injured areas...However, CSZYRG did not affect the skin microbial diversity of AD model mice but could exert an effect on the skin microbial community in AD mice and the relative abundance of the dominant microflora. CSZYRG may play a therapeutic role in AD by affecting the skin microbial community and relative abundance of dominant microflora in AD mice.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: Impact of fucosyltransferase 1-mediated epidermal blood group antigen H on anti-inflammatory response in atopic dermatitis. (Pubmed Central) - Jun 6, 2024
Therefore, we aim to investigate the expression of ABH antigens in skin tissue of patients with atopic dermatitis (AD) and MC903-induced AD-like mice...The infiltration of CD4+ T cells, eosinophils, and mast cells into the lesional skin was significantly elevated in Fut1-deficient mice compared with that in WT mice. These findings demonstrate the protective role of H2 antigen expression against AD-like inflammation and highlight its potential therapeutic impact on AD through the regulation of blood group antigens.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: Inhibition of macrophage MAPK/NF-?B pathway and Th2 axis by mangiferin ameliorates MC903-induced atopic dermatitis. (Pubmed Central) - May 11, 2024
In the present study, we reported that MAN could reduce inflammatory cell infiltration and scratching at the lesion site by decreasing MC903-induced levels of Th2-type cytokines, Histamine, thymic stromal lymphopoietin, Leukotriene B4, and immunoglobulin E. The mechanism may be related to reductions in MAPK and NF-?B-associated protein phosphorylation by macrophages. The results suggested that MAN may be a promising therapeutic agent for AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: Meteorin-like protein/METRNL/Interleukin-41 ameliorates atopic dermatitis-like inflammation. (Pubmed Central) - May 10, 2024
The results suggested that MAN may be a promising therapeutic agent for AD. METRNL can bind to KIT receptor and subsequently alleviate the allergic inflammation of AD by inhibiting the expansion of immune cells, and downregulating inflammatory gene expression by regulating the level of active WNT pathway molecule ?-Catenin.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Application of low-level laser with 1064nm Q-switched Nd: YAG laser may ameliorate atopic dermatitis (Poster Zone) - Apr 21, 2024 - Abstract #EAACI2024EAACI_2120;
Method Experimental AD mouse model triggered by topical application of MC903 was employed...Conclusion 1064-nm QS laser with the energy under LLLT ameliorates AD skin lesions and itch by inhibiting Th2 responses. 1064-nm QS laser can be considered a potential therapeutic choice for AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
The calpain/ABCA1 pathway drives mast cell- initiated vascular leakage and inflammation in the skin. (Exhibit Hall F1; Poster Board Number: B746) - Mar 29, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_1908;
Corroborating this finding, global ABCA1 blockade with FDA-approved glyburide similarly reduced inflammation induced by MC903. Collectively, these data suggest that targeting the calpain/ABCA1 pathway may open new therapeutic avenues for MC -mediated inflammation in the skin.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Novel Oral Treatment for Atopic Dermatitis: Allosteric Modulation of GABAA Receptor Signaling (Exhibit Hall F1; Poster Board Number: B646) - Mar 29, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_1261;
The administration of GABAA receptor ligands demonstrated a substantial reduction in ear inflammation, ear thickness, and ear scratching in the murine model for AD. This research provides promising insights into the development of a novel and effective oral treatment for AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
The calpain/ABCA1 pathway drives mast cell- initiated vascular leakage and inflammation in the skin. (Room W179) - Mar 22, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_389;
Corroborating this finding, global ABCA1 blockade with FDA-approved glyburide similarly reduced inflammation induced by MC903. Collectively, these data suggest that targeting the calpain/ABCA1 pathway may open new therapeutic avenues for MC -mediated inflammation in the skin.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression. (Pubmed Central) - Mar 17, 2024
A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls...Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
EOSINOPHILIC ESOPHAGITIS ALTERS THE EPITHELIAL AND IMMUNOLOGICAL LANDSCAPE TO LIMIT CARCINOGENESIS IN THE MURINE ESOPHAGUS (103AB - Walter E. Washington Convention Center) - Mar 14, 2024 - Abstract #DDW2024DDW_6041;
Continuing analysis will validate these findings in vivo and examine alterations in activation states of immune cells between conditions that may contribute to anti-tumorigenic activity associated with EoE inflammation. Furthermore, complete evaluation of differential gene expression as well chromatin availability can identify novel targets for therapeutic action in esophageal carcinoma.
- |||||||||| Jakafi (ruxolitinib) / Incyte, Dovonex (calcipotriol) / LEO Pharma, Novartis
A NOVEL STAT3/6-MEDIATED MITOCHONDRIAL-IMMUNE PATHWAY CONTRIBUTES TO EOE PATHOGENESIS (103AB - Walter E. Washington Convention Center) - Mar 14, 2024 - Abstract #DDW2024DDW_6036;
EoE was induced in mice using MC903/Ovalbumin (OVA) and peeled epithelium was evaluated for mitochondrial DNA (mtDNA) by qPCR and MTCO1 by immunoblotting...Ruxolitinib suppressed STAT6 Tyr 641 and STAT3 Ser 727 phosphorylation mediated by either IL-4 or IL-13... IL-13 and IL-4 in the EoE inflammatory milieu activate STAT3/6 signaling, increasing mitochondria in esophageal epithelial cells, and promoting EoE inflammation.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: Epidermal barrier impairment predisposes for excessive growth of the allergy-associated yeast Malassezia on murine skin. (Pubmed Central) - Feb 22, 2024
This study provides evidence that structural and metabolic changes in the dysfunctional epidermal barrier environment provide increased accessibility and an altered lipid profile, to which the lipid-dependent yeast adapts for enhanced nutrient assimilation. Our findings reveal fundamental insights into the implication of the mycobiota in the pathogenesis of common skin barrier disorders.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis, RGRN-305 / Regranion, MC2 Therap
Journal: Heat shock protein 90 inhibition attenuates inflammation in models of atopic dermatitis: a novel mechanism of action. (Pubmed Central) - Jan 30, 2024
Lastly, we discovered using Western blot that RGRN-305 disrupted JAK-STAT signaling by suppressing the activity of STAT3 and STAT6 in primary human keratinocytes, which was consistent with enrichment analyses from the mouse model. HSP90 inhibition by RGRN-305 robustly suppressed inflammation in experimental models mimicking AD, proving that HSP90 inhibition may be a novel mechanism of action in treating AD.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Journal: Resveratrol modulates the Nrf2/NF-?B pathway and inhibits TSLP-mediated atopic march. (Pubmed Central) - Jan 12, 2024
Phase classification: P2a --> P2 | Trial completion date: Nov 2026 --> Feb 2027 | Initiation date: Nov 2023 --> Feb 2024 | Trial primary completion date: Nov 2026 --> Feb 2027 Resveratrol attenuates TSLP-reduced atopic march through ameliorating inflammation and cell infiltration in pulmonary and ear skin tissues by inhibiting the abnormal activation of NF-?B signaling pathway.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: Study the involvement of Langerin in mediating epicutaneous sensitization of atopic dermatitis-like mouse model (Pubmed Central) - Nov 1, 2023
Together, our study indicates that autophagy is required for M2 activation and macrophage autophagy may be a promising target for AD intervention. Mice were topically treated with calcipotriol (MC903) plus ovalbumin (OVA) on the ears to establish AD mouse models, and mice were divided into wild-type control group, wild-type AD group, Langerin knockout control group, and Langerin knockout AD group...In Langerin knockout mice, compared to wild-type mice, skin erythema, skin tumidness, epidermal thickening, inflammatory cell infiltration were more obvious; the mRNA expression levels of Tslp, Il4, Il13, Il17a and Il22 were upregulated with (8.19
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Trial completion date, Trial initiation date, Trial primary completion date: Testing the Efficacy of Topical Calcipotriene Plus 5-Fluorouracil Combination to Activate the Immune System Against Precancerous Skin Lesions in Organ Transplant Recipients (clinicaltrials.gov) - Oct 26, 2023
P2a, N=56, Not yet recruiting,
Mice were topically treated with calcipotriol (MC903) plus ovalbumin (OVA) on the ears to establish AD mouse models, and mice were divided into wild-type control group, wild-type AD group, Langerin knockout control group, and Langerin knockout AD group...In Langerin knockout mice, compared to wild-type mice, skin erythema, skin tumidness, epidermal thickening, inflammatory cell infiltration were more obvious; the mRNA expression levels of Tslp, Il4, Il13, Il17a and Il22 were upregulated with (8.19 Trial completion date: Oct 2025 --> Nov 2026 | Initiation date: Jul 2023 --> Nov 2023 | Trial primary completion date: Oct 2025 --> Nov 2026
- |||||||||| Review, Journal: Noncorticosteroid Topical Therapies for the Treatment of Plaque Psoriasis: A Narrative Review. (Pubmed Central) - Sep 25, 2023
Data Sources: A literature search of the PubMed database was performed (January 1978 to May 2023) using the keywords plaque psoriasis, tapinarof, benvitimod, Vtama, roflumilast, Zoryve, pimecrolimus, tacrolimus, tazarotene, tacalcitol, calcitriol, Vectical, calcipotriene, Dovonex, tacalcitol, vitamin D analogs, salicylic acid, non-corticosteroid topical, Investigator's Global Assessment, and Physician's Global Assessment...The percentage of patients with plaque psoriasis who achieved Investigator's Global Assessment (IGA) success after 8 weeks of treatment with tacalcitol, calcipotriene/betamethasone dipropionate compound, tazarotene/halobetasol propionate, and roflumilast was 17.9%, 39.9%, 40.7%, and 42.4%, respectively...Each topical was efficacious in treating plaque psoriasis and had an adequate safety profile. Despite several treatment options for plaque psoriasis, medication adherence is a limiting factor.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Topical GZ21T attenuates skin lesions and pruritus in an atopic dermatitis preclinical model (e-Poster Hall) - Aug 30, 2023 - Abstract #EADV2023EADV_2667;
Mice of both groups were treated daily for 12 days with MC903 (4 nmol in 20 ml ethanol) on the right ear and ethanol (20 ml) on the left ear... These results indicate that GZ21T exhibits promising potential as a topical agent for the treatment of eczematous lesions and pruritus in AD.
- |||||||||| Eucrisa (crisaborole) / Pfizer
Preclinical, Journal: Crisaborole Inhibits Itch and Pain by Preventing Neutrophil Infiltration in a Mouse Model of Atopic Dermatitis. (Pubmed Central) - Aug 26, 2023
Calcium imaging of mouse dorsal root ganglion neurones revealed that pretreatment with S100A8/A9 significantly increased calcium responses to histamine and capsaicin, and the proportion of chloroquine-sensitive neurones. These findings suggest that the PDE4 inhibitor reduces itch and pain, in part by inhibiting infiltration of S100A8/A9-containing neutrophils in a mouse model of MC903-induced atopic dermatitis.
- |||||||||| Dovonex (calcipotriol) / LEO Pharma, Novartis
Preclinical, Journal: The Anti-Inflammatory and Skin Barrier Function Recovery Effects of Schisandra chinensis in Mice with Atopic Dermatitis. (Pubmed Central) - Aug 2, 2023
Furthermore, unlike dexamethasone, EESC did not reduce the spleen/body weight ratio. These results suggest that S. chinensis can be used as an alternative to external corticosteroids and that its anti-inflammatory and skin barrier dysfunction-restoring effects are related to the downregulation of pro-inflammatory cytokines and chemokines, such as TNF-?, IL-4, IL-6, IL-8, and TSLP.
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