A Single Subcutaneous Dose of BMD-1141 Stimulates Hair Regrowth Comparable to Daily, High-Dose Ruxolitinib in a Mouse Model of Alopecia Areata

Alopecia areata (AA) is an autoimmune disorder of hair loss resulting from a T-cell mediated attack on hair follicles. Three Janus kinase (JAK) inhibitors have been approved for the treatment of moderate-to-severe alopecia areata; however, safety concerns for immunosuppressive therapy have limited their use. We previously demonstrated that BMD-1141, consisting of parathyroid hormone (PTH) fused to a collagen-binding domain (CBD) (PTH-CBD) improved hair retention, increased anagen hair follicles counts, and reduced hair follicle dystrophy in C3H/HeJ-engrafted mice). We now compare the effects of a single subcutaneous injection of BMD-1141 with the daily, high-dose, oral administration of the JAK inhibitor ruxolitinib on anagen hair follicle counts and hair regrowth in C3H/HeJ-engrafted mice. BMD-1141-treated mice exhibited a significant increase in anagen hair follicle counts (<i>p</i> < 0.05) and enhanced hair regrowth compared to ruxolitinib-treated mice after 8 weeks. Hair follicles from the BMD-1141-treated mice showed increased beta-catenin, consistent with a mechanism of stimulating the anagen transition of hair follicles, and did not increase immune cell infiltration. Thus, a single subcutaneous dose of BMD-1141 stimulated hair regrowth comparable to daily ruxolitinib, apparently by stimulating the hair cycle, rather than inhibiting the autoimmune response.