Recent approaches of antibody therapeutics in androgenetic alopecia

Abstract

Therapeutic antibodies (Abs) have been anticipated as promising alternatives to conventional treatments such as topical minoxidil and oral finasteride for androgenetic alopecia (AGA). Due to the high molecular weight of typical Abs, the half-life of subcutaneous Abs exceeds 2 weeks, allowing an administration intervals of once a month or longer. Direct injection into the areas of hair loss is also feasible, potentially enhancing treatment efficacy while minimizing systemic side effects. However, therapeutic Abs are rarely developed for AGA therapy due to the requirement to be responsiveness to androgens and to exist in the extracellular fluid or cell surface surrounding the hair follicle. In this review, we introduce recent progress of antibody therapeutics in AGA targeting the prolactin receptor, Interleukin-6 receptor, C-X-C motif chemokine ligand 12, and dickkopf 1. As therapeutic Abs for AGA are still in the early stages, targets need further validation and optimization for clinical application.

Keywords: C-X-C motif chemokine ligand 12; androgenetic alopecia; dickkopf 1; interleukin-6 receptor; prolactin receptor; therapeutic antibody.

FIGURE 1

The structure of the skin and the movement of subcutaneously administered mAbs. The hypodermis consists of adipose and connective tissues interspersed with blood and lymphatic vessels. The connective tissues of the hypodermis are made up of highly polymerized macromolecular networks, and the vascular capillaries in the hypodermis are impermeable to large molecules (>50 kDa). Therefore, it is generally assumed that reaching from the hypodermis to systemic circulation results from lymphatic drainage for most mAbs. However, lymph flow is slower than 0.2% of blood flow, the systemic absorption of mAbs from injection site is limited.

FIGURE 2

Multi-functional role of CXCL12 for AGA therapy. Androgen hormones secrete CXCL12 from dermal fibroblasts (DF) via androgen receptor (AR). Secreted CXCL12 activates AR in DF and dermal papilla cells (DPCs), and miniaturized hair follicle. On the contrary, CXCL12 Ab inactivates AR in DF and DPCs, and inhibits inflammation and fibrosis surrounding hair follicle.