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Nrp1 a potential new target for psoriasis Tx

Researchers from Université Libre de Bruxelles in Brussels, Belgium, have identified a potential new therapeutic target for the prevention of psoriasis lesions.

In a paper published in Science Advances (Jan. 8, 2020; 6(2):eaax5849), the authors detail how in mouse models of psoriasis, conditional deletion of the tyrosine kinase receptors Flt1 (VEGFR1) and Flk1 (VEGFR2) inhibited expression of vascular endothelial growth factor A (VEGFA), which is known to contribute to psoriasis by encouraging vascularization in the skin.

“It was very surprising to find that inhibiting VEGFA signalling only in the epidermis was sufficient to completely prevent psoriasis development including immune cell infiltration and increase in blood vessel formation mediated by VEGFA over-expression,” said Dr. Farida Benhadou, the first author of this study, in a press release.

Dr. Benhadou is an MD and PhD student at the department of dermatology and venereology, Université Libre de Bruxelles, and works at the Erasme Hospital in Brussels, and the laboratory of Stem cells and cancer (Blanpain Lab) at Université Libre de Bruxelles.

To determine if there could be therapeutic value in inhibiting Neuropilin 1 (Nrp1), which acts as a VEGFA co-receptor, the research team administered anti-Nrp1 antibody to block the interaction between Nrp1 and VEGFA in mice presenting with psoriasis. Administration of the antibody resulted in a rapid disappearance of the lesions.

“These data demonstrate the therapeutic benefit of blocking Vegfa/Nrp1 interaction in the treatment of psoriatic disease, which may be safer for the treatment of psoriasis as compared to other therapeutic modalities that can be associated with serious side effects,” said Dr. Cédric Blanpain, the senior author of this study. Dr. Blanpain is tenured professor of developmental biology and genetics at Université Libre de Bruxelles and director of the stem cell and cancer lab at its Faculty of Medicine

According to the release, this study demonstrates the essential role of Flt1 and Nrp1 expression in the skin epidermis in mediating psoriasis development, and the findings have important implications for the understanding of mechanisms leading to psoriasis, and for development of treatments.

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