Effect of systemic exposure of JAK1 Inhibition (AZ13748709) in C3H/HeJ Mice with Alopecia Areata In Vivo

JAK inhibition by means of clinically available pan JAK inhibitors has recently demonstrated great efficacy in both restoring hair growth and resolving inflammation in the skin of patients with Alopecia Areata (AA). These effects are dose dependent and mainly efficacious at ranges close to a questionable risk profile. Given the great responses to JAK inhibition and the current lack of efficacious treatments in AA, it is exciting to explore the possibilities to separate the beneficial and adverse effects in order to provide a successful treatment option for these patients where the medical need is still vastly unmet. We have demonstrated that specific inhibition of JAK1 at relevant concentrations produces a fast resolution of inflammation and complete restoration of hair growth in the C3H/HeJ model of AA and importantly, that systemic exposure is essential for efficacy. Overall design: 4 groups: Healthy, Alopecia, syst JAK1i, 8w off Tx. The aim of the present study is to evaluate hair growth as well as the skin ALADIN score and histopathological evaluation after 12 weeks of oral administration of the JAK1 selective antagonist AZ13748709 in C3H/HeJ mice with severe alopecia areata.