Targeting Selectin Functions in the Therapy of Psoriasis
Potential strategies to interfere with selectin functions include direct inhibition through monoclonal antibodies or small-molecule compounds, transcriptional regulation of selectin expression, and modulation of the post-transcriptional glycosylation of selectin ligands. More than a dozen different compounds targeting selectin functions are currently under development, several of which have shown promising effects on leukocyte recruitment and the therapy of inflammatory conditions under experimental conditions. However, based on preclinical and early clinical investigations, it appears that in some cases specifically targeting the function of single selectins may not be sufficient to effectively interrupt the inflammatory cascade. This is, at least in part, due to considerable redundancies and overlaps in the functions of the selectins, a notion that is corroborated by the apparently more pronounced therapeutic efficacy of some compounds with broader activity against several selectins.
Overall, while targeting selectin functions promises rather selective and pathogenesis-based therapeutic approaches against psoriasis, the clinical value of such strategies, alone or in combination with other therapies, remains to be seen.
Document Type: Review Article
Affiliations: Rudolf Virchow Center,DFG Center for Experimental Biomedicine and Department of Dermatology and Venereology, Julius Maximilians University, Versbacher Str. 9, 97078 Würzburg, Germany.
Publication date: June 1, 2004