Therapeutics: Silencing psoriasis

Crow, James Mitchell

doi:10.1038/492s58a

Cited by 30 publications

(33 citation statements)

References 6 publications

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“…The therapies introduced by Abbott, Amgen and Janssen are clinically effective and have side effects that do not lead to significant risk of infections [20]. However, current approaches can be improved by better understanding the molecular progression of plaque psoriasis and developing future therapies to target immune cell receptors, chemokines and additional agents within the inflammatory cascade.…”

Section: Current and Future Therapiesmentioning

confidence: 99%

“…Similarly, Amgen has developed etanercept, an anti-TNF-a dimeric fusion protein to treat moderate-to-severe psoriasis [20]. In addition, Janseen Biotech has developed infliximab, which is a mouse-human chimeric anti-TNF-a mAb-based drug to treat psoriasis and psoriatic arthritis [20].…”

Section: Current and Future Therapiesmentioning

confidence: 99%

“…Specifically, anti-TNF-a monoclonal antibodies (mAbs) target cytokines, the p40 shared domain of IL-12 and IL-23 and the anti-inflammatory pathway. Abbott Laboratories has developed adalimumab, which is a fully human anti-TNFa mAb, as a therapeutic drug that has been approved by US FDA to treat plaque psoriasis [20]. Similarly, Amgen has developed etanercept, an anti-TNF-a dimeric fusion protein to treat moderate-to-severe psoriasis [20].…”

Section: Current and Future Therapiesmentioning

confidence: 99%

“…These therapies include topical agents, systemic therapies and biological drugs to combat the key agents within the inflammatory cascade. In the past 25 years, significant research has been done on using biological immunosuppressant therapies, and it has been shown to be effective within late phase clinical trials [20]. Specifically, anti-TNF-a monoclonal antibodies (mAbs) target cytokines, the p40 shared domain of IL-12 and IL-23 and the anti-inflammatory pathway.…”

Section: Current and Future Therapiesmentioning

confidence: 99%

“…Abbott Laboratories has developed adalimumab, which is a fully human anti-TNFa mAb, as a therapeutic drug that has been approved by US FDA to treat plaque psoriasis [20]. Similarly, Amgen has developed etanercept, an anti-TNF-a dimeric fusion protein to treat moderate-to-severe psoriasis [20]. In addition, Janseen Biotech has developed infliximab, which is a mouse-human chimeric anti-TNF-a mAb-based drug to treat psoriasis and psoriatic arthritis [20].…”

Section: Current and Future Therapiesmentioning

confidence: 99%

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Psoriasis and lasting implications

Raju

2013

Expert Review of Clinical Immunology

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Section: Current and Future Therapiesmentioning

confidence: 99%

Section: Current and Future Therapiesmentioning

confidence: 99%

Section: Current and Future Therapiesmentioning

confidence: 99%

Section: Current and Future Therapiesmentioning

confidence: 99%

Section: Current and Future Therapiesmentioning

confidence: 99%

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Psoriasis and lasting implications

Raju

2013

Expert Review of Clinical Immunology

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Epigenetic treatment of dermatologic disorders

Moos

Faller

Glavas

et al. 2019

Drug Development Research

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Healthy skin protects us against a multitude of insults, but injured or maladapted skin can lead to infection, inflammation, or worse. Fortunately, naturally occurring bioactive products, many commonly found in olive oil and other plant and vegetable extracts, have shown utility in treating skin and related diseases as well as conditioning the skin to maintain its healthy function. Powerful agents targeting nuclear regulatory pathways continue to hold promise as new or repurposed therapies for a wide variety of ills and skin conditions. Epigenetic approaches that activate Nrf2 to effect detoxification, redox balance, DNA repair, and mitochondrial function are noteworthy. Some of the disease applications being actively investigated range from eczema and psoriasis to skin cancer and diabetes‐related wound healing to name just a few.

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Control of late cornified envelope genes relevant to psoriasis risk: upregulation by 1,25-dihydroxyvitamin D3 and plant-derived delphinidin

et al. 2013

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Psoriasis is a chronic inflammatory skin disease featuring abnormal keratinocyte proliferation and differentiation. A genetic risk factor for psoriasis (PSORS4) is a deletion of LCE3B and LCE3C genes encoding structural proteins in terminally differentiated keratinocytes. Because analogs of 1,25-dihydroxyvitamin D3 (1,25D) are used in psoriasis treatment, we hypothesized that 1,25D acts via the vitamin D receptor (VDR) to upregulate expression of LCE 3A/3D/3E genes, potentially mitigating the absence of LCE3B/LCE3C gene products. Results in a human keratinocyte line, HaCaT, suggested that 1,25D, low affinity VDR ligands docosahexaenoic acid and curcumin, along with a novel candidate ligand, delphinidin, induce LCE transcripts as monitored by qPCR. Further experiments in primary human keratinocytes preincubated with 1.2 mM calcium indicated that 1,25D and 10 μM delphinidin upregulate all five LCE3 genes (LCE3A-E). Competition binding assays employing radiolabeled 1,25D revealed that delphinidin binds VDR weakly (IC50 ≈ 1 mM). However, 20 μM delphinidin was capable of upregulating a luciferase reporter gene in a VDRE-dependent manner in a transfected keratinocyte cell line (KERTr). These results are consistent with a scenario in which delphinidin is metabolized to an active compound that then stimulates LCE3 transcription in a VDR/VDRE-dependent manner. We propose that upregulation of LCE genes may be part of the therapeutic effect of 1,25D to ameliorate psoriasis by providing sufficient LCE proteins, especially in individuals missing the LCE3B and 3C genes. Results with delphinidin further suggest that this compound or its metabolite(s) might offer an alternative to 1,25D in psoriasis therapy.

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Therapeutics: Silencing psoriasis

Cited by 30 publications

References 6 publications

Psoriasis and lasting implications

Psoriasis and lasting implications

Epigenetic treatment of dermatologic disorders

Control of late cornified envelope genes relevant to psoriasis risk: upregulation by 1,25-dihydroxyvitamin D3 and plant-derived delphinidin

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