BioCentury
ARTICLE | Distillery Therapeutics

Dermatology

August 8, 2018 11:53 PM UTC

Mouse studies suggest inhibiting the TRPA1-miR-711 interaction could help treat lymphoma-associated itch. In skin samples from a mouse model of lymphoma, the number of cells expressing miR-711 was higher than in normal mice, and in silico docking of miR-711 with the itch-regulating ion channel TRPA1 identified binding interactions between miR-711 and the extracellular loops of TRPA1, including the S5-S6 loop. In a mouse model of miR-177-induced chronic itch, intradermal injection of an antisense RNA oligonucleotide targeting miR-711 or a peptide from the S5-S6 loop of TRPA1 decreased the frequency of scratching behaviors compared with vehicle or an inactive mutant version of the peptide. In a xenograft mouse model of cutaneous T cell lymphoma (CTCL)-associated chronic itch, tumor-specific expression of the anti-miRNA-711 oligonucleotide or intratumoral injection of the TRPA1 peptide decreased the frequency of scratching behaviors compared with no treatment or the inactive mutant peptide, respectively. Next steps include identifying and testing additional RNA-based or small molecule TRPA1 inhibitors in the models. ...

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