Selective Janus kinase 1 inhibition resolves inflammation and restores hair growth offering a viable treatment option for alopecia areata

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. Selective JAK1 inhibition mainly affects genes downstream of STAT1, STAT3 & STAT6 in human immune cells. Importantly, pathways like T-cell differentiation and lymphopoiesis are less affected by the selective JAK1 inhibitor versus less specific JAK inhibitors like tofacitinib and ruxolitinib. These findings indicate that it is feasible to develop more selective and specific JAK1 inhibitors that are as efficacious as pan-JAK inhibitors but with a better safety profile as systemic exposure is mandatory for efficacy in this disease. Overall design: Peripheral blood CD8+ T-cells from 4 healthy donors were stimulated in vitro for 40hrs with plate bound anti-CD3 (OKT3) in complete media in the presence or absence of different JAK inhibitors: tofacitinib, ruxolitinib and a selective JAK1 inhibitor at 300 nM. Soluble anti-CD28 were added to the CD8+ cultures to facilitate co-stimulation.