Innovative strategies for the discovery of new drugs against androgenetic alopecia
- PMID: 40029254
- DOI: 10.1080/17460441.2025.2473905
Innovative strategies for the discovery of new drugs against androgenetic alopecia
Abstract
Introduction: Androgenetic alopecia (AGA) is the most common cause of hair loss worldwide. The significant psychological and social impact of AGA continues to drive demand for more effective treatments beyond the limited options currently available.
Areas covered: The authors review the key components of AGA pathogenesis, as well as current treatments, and therapeutic techniques under development. Innovative strategies for AGA drug discovery are still needed, given the significant unmet medical needs and the limited efficacy of both current and emerging treatments. The authors outline relevant preclinical models, such as hair follicle (HF) cell cultures, 3D spheroids, organoids, follicle explants, and animal models, highlighting their advantages and limitations in AGA research. Finally, they summarize the primary objectives in AGA treatment development, including direct hair growth promotion, interference with androgen signaling, and HF rejuvenation, identifying key pathogenesis intervention points for treatment development.
Expert opinion: Developing better in vitro models, possibly using induced pluripotent stem cell (iPSC) systems, could greatly accelerate drug discovery. Similarly, a superior in vivo model could significantly expedite drug discovery. Near future development research should focus on drug delivery improvements. Longer term, treatments targeting AGA's underlying pathophysiology and promoting HF rejuvenation or true regeneration would provide the most benefit to prospective patients.
Keywords: Androgenetic alopecia; baldness; disease models; disease pathogenesis; drug development; hair regrowth; pattern hair loss; pre-clinical models.
Plain language summary
Androgenetic alopecia (AGA), typically called male/female pattern baldness, is the most common type of hair loss worldwide. It is caused by the action of androgen hormones targeting cells in hair follicles and causing them to age prematurely and eventually die off. AGA can have a significant negative psychological and social impact on those affected. Current treatments are limited, often not very effective, and carry the risk of side effects, leading to a demand for better therapeutic options by both patients and clinicians.This article reviews the key factors that cause AGA, existing treatments, and new therapies being developed. The authors discuss different laboratory models used to study AGA, like cultures of hair follicle cells, 3D cell clusters (called spheroids and organoids), whole hair follicles and scalp skin donated by volunteers, and animal models of hair growth and alopecia. The authors highlight the strengths and weaknesses of the models to help researchers select the ones most suitable for their drug development studies. They also outline the main goals in developing new AGA treatments: namely directly promoting hair growth, blocking the effects of androgens, or rejuvenating damaged hair follicles.The authors suggest that creating better lab models, possibly using induced pluripotent stem cells (iPSCs), could speed up drug discovery for AGA. Improving how drugs are delivered to the scalp could help in the near future. In the longer term, treatments that address the underlying causes of AGA, restoring hair follicle size and increasing scalp hair follicle density, would be most beneficial for patients.
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