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 high-dose (5 mg/ml) clinical study, AR68 was given once per week for 24 weeks and showed 83% efficacy in increasing hair counts compared with finasteride. No side effects were observed. Therefore, SAMiRNA targeting AR mRNA is a potential novel topical treatment for AGA.
Subject(s)
MicellesABSTRACT
BACKGROUND: The skin brightness is determined according to the amount and type of melanin. People with darker skin have a greater amount of melanin that makes their skin less susceptible to UV damages. They live in lower latitude and receive a greater amount of the intensity of the UV radiation. AIM: We wanted to know how the latitude and skin brightness affect skin aging. METHODS: Three thousand volunteers from seven countries (Korea, China, India, Thailand, Vietnam, Indonesia, and Malaysia), aged 20-59 years, participated in this study. We measured skin brightness, Ra (wrinkles parameter), and R2 (elasticity parameter) under controlled environmental conditions. The skin brightness of the face was measured using the Janus® which is a facial analysis system. Cutometer® the elasticity was measured by on the cheeks, and PRIMOS lite® was used to evaluate wrinkles on crow's feet. RESULTS: Latitude and skin brightness showed a positive correlation (0.346). Also, the correlations of Ra and R2 with skin brightness were significantly negative (-0.181) and positive (0.105), respectively. Results of comparison of Ra and R2 with age among the countries showed no significant difference among the 20s, but there was a significant difference among the 50s between countries with high latitude and low latitude. CONCLUSION: The long-term exposure of UV radiation, the natural environmental factor, seems to have more decisive effect on the skin aging process than the photoprotective effect of melanin of epidermal skin. This study helps to understand differences of the skin properties among countries in Asia.
