In vitro and in vivo models for androgenetic alopecia drug development

Alopecia is a common disorder that can cause hair loss owing to various factors, including genetics, stress and diet. Androgenetic alopecia (AGA), also known as male pattern baldness, is the most common type of progressive hair loss. AGA symptoms can be alleviated by effective drugs, such as finasteride and minoxidil. Therefore, most patients with alopecia select drug therapy as the first-line treatment. However, their side effects and variable efficacy have increased the demand for alternative treatment options for these patients. Despite the high clinical demand, the development of novel therapeutic agents remains limited, primarily due to the lack of physiologically relevant drug testing models that accurately predict drug effects in humans. In this At a Glance article, we provide an overview of the currently available in vitro models for hair drug testing. First, we outline the limitations of traditional models, such as two-dimensional cultures and animal models, in reproducing hair follicle structures and multicellular signaling pathways. We then introduce three-dimensional culture platforms that partially overcome these drawbacks. Next, we discuss the differences and applications of various models in terms of functional readouts, reproducibility, high-throughput potential, standardization and cost. We highlight recent progress in the development of follicular skin model constructs and propose practical metrics for selecting the most appropriate model for the initial screening of potential hair drugs. Overall, this At a Glance article provides a roadmap towards a more translationally valuable screening system for the discovery and development of hair loss treatments.