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: Obesity is associated with diabetes mellitus, hypertension, dyslipidemia and increased cardiovascular disease (CVD) risk. Anthropometric indices, such body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR), were evaluated as predictors of the presence of CVD risk factors in Korean adults. METHODS AND RESULTS: The data were obtained from the Third Korea National Health and Nutrition Examination Survey (KNHANES III, 2005). The study contained a nationally representative sample of Korean adults (2,327 men, 3,102 women) aged 20 years or older. The area under the receiver operating characteristic (ROC) curve for WHtR was higher than that for WC or BMI with respect to diabetes mellitus and hypertension in both men and women, whereas WC was a better predictor for low high-density lipoprotein cholesterol in men. The WHtR cut-off value to predict diabetes mellitus, hypertension, and dyslipidemia was approximately 0.50 in men and 0.51 in women. The WC cut-offs varied from 81.6 to 85.2 cm in men and from 78.1 to 81.9 cm in women. The optimal BMI cut-off point varied from 23.0 to 24.7 kg/m(2) in both men and women. CONCLUSIONS: WC or WHtR may be a better predictor of CVD risk factors than BMI in Korean adults.
