570 Targeting JAK/STAT and Wnt/b-catenin pathways and 5a-reductase activity to develop an effective anti-hair loss product

Abstract

Androgenetic alopecia (AGA) is a multi-cause pathology resulting in hair cycle deregulation and production of short, fine hair. New insights into hair follicle biology and understanding of AGA have brought new strategies to treat it. The aim of this study was to demonstrate the interest of using ingredients targeting well-known and innovative biological targets to develop an effective anti-hair loss product. The active ingredients were evaluated on their ability to regulate the hair cycle. Activation of the Wnt/b-catenin pathway in hair follicle dermal papilla cells (HFDPC) was assessed using a reporter gene assay strategy. Inhibition of interleukine-6-induced JAK/STAT pathway activation in outer root sheath keratinocytes (ORSK) was assessed by measuring STAT3 phosphorylation. Conversion of testosterone (T) to DHT by the enzyme 5a-reductase (5aRed) in HFDPC was assessed by analysing T metabolism using radiolabelled T. A lotion containing these ingredients was tested on 60 subjects for 3 months, 2 applications per week for 1 month then 1 application per week for the following 2 months. The anagen/telogen (A/T) ratio was assessed by phototrichogram analysis. The combination of Nasturtium officinale and Tropaeolum majus extracts increased the activation of Wnt/b-catenin by 38% in HFDPC. Garcinia Mangostana extract significantly reduced JAK/STAT activation in ORSK by 33%. Glyceryl laurate significantly reduced T to DHT conversion by 42% suggesting that 5aRed activity was inhibited. When tested on 60 subjects, the lotion significantly increased the number of anagen hairs in subjects’ scalp and the A/T ratio, and also significantly decreased the number of telogen hairs after 3 months of treatment. Hair follicle biology is an ever-evolving science and targeting newly described biological pathways such as the JAK/STAT pathway with well-chosen ingredients will provide patients with effective anti-hair-loss solutions matching their needs and expectations.