Researchers have identified that non-peptidic oxytocin receptor (OXTR) agonists, LIT001 and WAY267464, show promise as potential treatments for alopecia by promoting hair growth. The study, published in Scientific Reports, highlights the role of OXTR activation in dermal papilla (DP) cells and its impact on hair follicle development.
The research addresses the limitations of using oxytocin itself, such as low receptor binding specificity and potential side effects, by exploring specific OXTR agonists. LIT001 and WAY267464, while having molecular weights slightly above the optimal range for skin penetration, can still reach DP cells through hair follicle pores, making them viable candidates for topical application.
OXTR Expression and Hair Growth
Bioinformatic analysis revealed that patients with alopecia have low OXTR expression levels in DP cells. Further experiments showed that OXTR knockdown in DP cells suppressed the expression of genes related to hair growth, suggesting a direct link between OXTR levels and hair follicle health.
In Vitro Studies with OXTR Agonists
In vitro studies demonstrated that both WAY267464 and LIT001 increased the expression of hair growth-related genes in DP cells. Additionally, these agonists accelerated the elongation of hair follicles sprouting from hair follicloids, indicating a positive impact on hair follicle development.
Comparison with Minoxidil
While both WAY267464 and LIT001 promoted hair follicle elongation, their effects were less pronounced than those of minoxidil, a well-established hair growth treatment. The researchers suggest that optimizing culture conditions, including drug concentration and timing, and combining OXTR agonists with minoxidil, which has a different mechanism of action, could enhance the hair growth effect.
Future Directions
The study highlights the need for further research to validate these findings through organ culture and animal models. Future studies should focus on: (i) prolonging the anagen phase or inhibiting the catagen phase; (ii) promoting proliferation or inhibiting apoptosis in the hair matrix; (iii) regulating important hair growth mediators at the protein expression level; (iv) observing OTXR-specific effects of WAY267464 and LIT001, with significant antagonization documented by OTXR silencing. Additionally, future research should evaluate the efficacies of WAY267464 and LIT001 using donor cells isolated from patients with alopecia.
Potential Therapeutic Strategy
These findings suggest that targeting OXTR with specific agonists represents a promising therapeutic strategy for hair loss. The study paves the way for the development of novel treatments that can effectively promote hair growth by modulating OXTR signaling in DP cells.
