Janus kinase inhibitors have been used to treat alopecia areata, but Janus kinase 2 inhibitors tend to cause adverse effects. Selective Janus kinase 1 inhibition was shown to be a promising and effective treatment in a mouse model of alopecia areata and in vitro human cells.
Janus kinase (JAK) inhibitors have been shown in previous research to be at least somewhat therapeutically effective in treating alopecia areata (AA). This treatment both restores hair growth and reduces inflammation in a way that is dose-dependent but has some adverse side effects. This is further complicated because JAK inhibitors are usually efficacious at ranges close to a questionable risk profile, which can make deciding on this treatment option complex for patients and their doctors.
This article, published in the journal Skin Health and Disease, explores the possibility of separating the positive and negative effects of JAK inhibition. This is done by selectively inhibiting JAK1 in order to avoid the adverse effects that are commonly associated with JAK2 inhibition.
Experimental JAK1 Inhibition in a Mouse Model of AA and In Vitro Human Cells
The C3H/HeJ mouse model of AA was used to understand the therapeutic efficacy in vivo with different regimens of JAK inhibition, including systemic versus local drug exposure. In order to selectively inhibit JAK1, topical vs. systemic exposure was explored. The treatment used small molecule JAK1 inhibitors with good bioavailability in systemic exposure or excellent tissue retention, as this can reduce some of the side effects of JAK1 inhibition. Twelve mice in total were used in the study, with six treated systemically for four weeks and six treated topically for 12 weeks.
In vitro human cells were also used in the study. These were stimulated with plate bound anti-CD3 in complete media, in the presence and absence of different JAK inhibitors, including tofacitinib and ruxolitinib.
JAK1 Inhibition Is Promising, but Still in an Early Stage of Research
Selective JAK1 inhibition was shown to quickly reduce inflammation and completely restore hair growth in mice, but topical treatment did not restore hair growth. Treatment also needed to extend beyond the time of hair growth in order to reach remission without treatment. Translation to human disease showed that the cytokines involved in AA were inhibited by selective JAK1 inhibition. Although still in an early stage of research, this model of JAK1 inhibition is a promising way to treat AA. JAK1 inhibition seems to have a superior safety profile compared to pan-JAK inhibitors.
Mattsson, J., Israelsson, E., Björhall, K., Yrlid, L. F., Thörn, K., Thorén, A., Toledo, E. A., Jinton, L., Öberg, L., Wingren, C., Tapani, S., Jackson, S. G., Skogberg, G., Lundqvist, A. J., Hendrickx, R., Cavallin, A., Österlund, T., Grimster, N. P., Nilsson, M., & Åstrand, A. Selective Janus kinase 1 inhibition resolves inflammation and restores hair growth offering a viable treatment option for alopecia areata. Skin Health and Disease, n/a(n/a), e209. https://doi.org/https://doi.org/10.1002/ski2.209