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Retinoids for the treatment of psoriasis: outlook for the future
1Department of Dermatology, University Hospital, Geneva, Switzerland.
Abstract:
Despite the demonstrated clinical success of retinoid therapy in psoriasis, its mechanism of action has not been fully elucidated, and investigators are confronted with two paradoxes. Firstly, the binding of retinoids to nuclear retinoic acid receptors (RARs) does not match their therapeutic efficacy. Secondly, formation of retinoic acid is probably increased in the psoriatic lesions. Answering these questions should result in: (i) the better use of acitretin, an oral synthetic retinoid, and tazarotene, the first compound for topical use; (ii) the development of new retinoids with specific pharmacological profile such as subtype-selective retinoids including molecules with an 'antiretinoid' activity and dissociating antiproliferative retinoids; and (iii) the better characterization of non-genomic effects of retinoids.
Insights
Retinoid therapy is effective for psoriasis, but its mechanism remains unclear. Research aims to resolve paradoxes in retinoid receptor binding and local retinoic acid levels for improved treatments.
Area of Science:
- Dermatology
- Molecular Biology
- Pharmacology
Background:
- Retinoid therapy shows clinical success in treating psoriasis.
- The precise mechanism of action for retinoids in psoriasis is not fully understood.
- Two paradoxes challenge current understanding: mismatched receptor binding and efficacy, and elevated retinoic acid in lesions.
Purpose of the Study:
- To elucidate the mechanism of retinoid action in psoriasis.
- To address discrepancies between retinoid binding to nuclear retinoic acid receptors (RARs) and therapeutic outcomes.
- To investigate the role of increased retinoic acid formation in psoriatic lesions.
Main Methods:
- Analysis of retinoid binding affinity to RARs.
- Quantification of retinoic acid levels in psoriatic lesions.
- Characterization of retinoid effects, including potential non-genomic actions.
Main Results:
- Observed a disconnect between retinoid binding to RARs and clinical efficacy.
- Indicated a probable increase in retinoic acid formation within psoriatic lesions.
- Highlighted the need to explore non-genomic effects of retinoids.
Conclusions:
- Resolving these paradoxes will optimize the use of existing retinoids like acitretin and tazarotene.
- Further research can lead to novel retinoids with specific pharmacological profiles, including subtype-selective and 'antiretinoid' agents.
- A deeper understanding of non-genomic retinoid effects is crucial for developing more targeted psoriasis therapies.