Weekly treatment with SAMiRNA targeting the androgen receptor ameliorates androgenetic alopecia

Sung-Il Yun,Woorim Choi,Oh Seung Kwon,Eun-Ah Goh,Seung Sik Lim,Sang-Kyu Lee,Han-Oh Park,Gaewon Nam,Mi Sun Lee,Soon Ja Choi,Jangseon Kim,Tae Kee Moon,Keeyeol Kyong,Sin Hae Kim

doi:10.1038/s41598-022-05544-w

Sung-Il Yun, Woorim Choi + Show 12 more

Open Access

https://doi.org/10.1038/s41598-022-05544-w

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Journal: Scientific Reports	Publication Date: Jan 31, 2022
Citations: 7	License type: open-access

Affiliation: Seowon University

Abstract

Androgenetic alopecia (AGA) is the most common type of hair loss in men and women. Dihydrotestosterone (DHT) and androgen receptor (AR) levels are increased in patients with AGA, and DHT-AR signaling correlates strongly with AGA pathogenesis. In this study, treatment with self-assembled micelle inhibitory RNA (SAMiRNA) nanoparticle-type siRNA selectively suppressed AR expression in vitro. Clinical studies with application of SAMiRNA to the scalp and massaging to deliver it to the hair follicle confirmed its efficacy in AGA. For identification of a potent SAMiRNA for AR silencing, 547 SAMiRNA candidates were synthesized and screened. SAMiRNA-AR68 (AR68) was the most potent and could be efficiently delivered to human follicle dermal papilla cells (HFDPCs) and hair follicles, and this treatment decreased the AR mRNA and protein levels. We confirmed that 10 µM AR68 elicits no innate immune response in human PBMCs and no cytotoxicity up to 20 µM with HFDP and HaCaT cells. Clinical studies were performed in a randomized and double-blind manner with two different doses and frequencies. In the low-dose (0.5 mg/ml) clinical study, AR68 was applied three times per week for 24 weeks, and through quantitative analysis using a phototrichogram, we confirmed increases in total hair counts. In the 24-week long high-dose (5 mg/ml) clinical study, AR68 showed average additional hair growth of 1.3-1.9 hairs/cm2 per month, which is comparable to finasteride. No side effects were observed. Therefore, SAMiRNA targeting AR mRNA is a potential novel topical treatment for AGA.

Highlights

Androgenetic alopecia (AGA), commonly known as male pattern hair loss (MPHL) in men and female pattern hair loss (FPHL) in women, is the most common type of progressive hair loss[1,2,3]
For potent self-assembled micelle inhibitory RNA (SAMiRNA) targeting androgen receptor (AR), SAMiRNAs containing 19 base pairs of DNA/RNA heteroduplexes were designed by the sliding window algorithm and selected for specificity for AR mRNA
The silencing effect of AR in LNCaP cells was analyzed for each SAMiRNA candidate by reverse transcription-quantitative polymerase chain reaction (RT-qPCR)

Summary

Introduction

Androgenetic alopecia (AGA), commonly known as male pattern hair loss (MPHL) in men and female pattern hair loss (FPHL) in women, is the most common type of progressive hair loss[1,2,3]. The best way to block DHT-AR signaling without inhibition of systematic DHT synthesis is suppression of AR expression in hair tissue alone This method constitutes an appropriate strategy for AGA treatment with minimal side effects. SAMiRNA is a new type of siRNA nanoparticle that does not result in innate immune stimulation. SAMiRNA nanoparticles do not show innate immune stimulation effects, unlike conventional siRNA formulations. SAMiRNA may be an ideal solution to overcome the above two problems of siRNA in the development of AGA treatment. Based on this theoretical background, we performed the following analyses

Methods

Results

Conclusion