Self-assembling peptide inspired by insulin and type 1 insulin-like growth factor for the treatment of androgenetic alopecia

Androgenetic alopecia (AGA), the most prevalent form of hair loss, urgently requires breakthroughs in existing therapies due to limitations such as medication side effects, recurrence risks, and treatment inefficacy. Herein, we propose an insulin-derived self-assembling sequence Ac-GFFY, combined with the C domain peptide of insulin-like growth factor 1, successfully designing an IGF-1 biomimetic peptide factor, Ac-GFFY-IGF, which can substitute for the absent IGF-1 in the AGA pathological environment and facilitate hair regrowth. Compared with IGF-1, Ac-GFFY-IGF exhibits superior in vitro stability and enhanced skin permeability. In the murine AGA model, Ac-GFFY-IGF demonstrated superior efficacy to the clinically used minoxidil, achieving faster hair regeneration, higher hair quality, and broader hair coverage at lower concentrations. Our strategy provides a critical theoretical foundation and technical pathway for developing novel mechanism-driven therapies for AGA. An IGF-1 mimetic peptide, which structurally and functionally mimics insulin-like growth factor-1 (IGF-1), activates phosphorylation of the IGF-1 receptor (IGF-1R) and downstream PI3K/AKT signaling pathway, promotes proliferation of dermal papilla (DP) cells, resists dihydrotestosterone (DHT)-induced apoptosis, facilitates the transition of hair follicles from telogen to anagen phase, and ultimately promotes hair regeneration in androgenetic alopecia (AGA) mouse models. • Ac-GFFY-IGF was designed as an IGF-1 mimetic with enhanced stability and skin permeability. • Ac-GFFY-IGF promotes hair regrowth more effectively than minoxidil and native IGF-1. • Ac-GFFY-IGF is a novel, safe and effective non-hormonal topical treatment for AGA.