Microneedling Immunosuppressants for Alopecia Areata Hair Regrowth

Alopecia areata (AA) is an autoimmune disease affecting approximately 160 million people worldwide.¹ With AA, the immune system attacks hair follicles, resulting in hair loss and preventing hair regrowth.² The standard approach to treating severe AA involves systemic immunosuppression with Janus kinase (JAK) inhibitors, which has demonstrated strong efficacy.³ However, researchers at Brigham and Women’s, Harvard, and MIT have invented a new method without systemic immunosuppression to teach the immune system not to attack the hair follicles.⁴ This prevents hair loss and allows for future hair regrowth in animal models of the disease.⁴

Immunology of Alopecia Areata
The hair follicle is an immune-privileged site where T cells cannot normally invade.² However, in AA, there is a collapse of this immune privilege around the hair follicle, resulting in the exposure of T cells to autoantigens.² This leads to an accumulation of auto-reactive CD8+ cytotoxic T cells (Tc1) and CD4+ T helper (Th1) cells, which attack the hair follicle and lead to hair loss.² As some T cells become autoreactive to the hair follicle antigens, they produce cytokines to encourage T cell autoreactivity and promote inflammation.² One of the critical cytokines in this process is interferon-ɣ (IFNɣ).² The current leading treatments for severe AA are JAK inhibitors, which work by blocking signaling via the JAK-STAT pathway, reducing the over-production of IFNɣ and preventing T cells from becoming autoreactive.³ The approved JAK inhibitors for severe AA are systemic treatments, resulting in global immunosuppression in the body.³ 

What Makes This Potential Treatment Different?
Scientists at Brigham and Women’s, Harvard, and MIT joined forces to invent a microneedle patch that suppresses local inflammatory T cell responses at the hair follicles and teaches the T cells to not react to hair follicle antigens.⁴ The patch secretes CCL22, a chemokine that attracts CD4+ T regulatory cells (Tregs), and IL-2 to support Treg function and survival.⁴

Using a mouse model of AA, the authors showed that an increased number of Tregs resulted in sustained hair regrowth and attenuated inflammation.⁴ With a humanized skin transplant mouse model, the authors showed that Treg expansion can also occur in human skin without causing peripheral immunosuppression.⁴

Translational Applications
This method of drug delivery for AA treatment shows translational promise, as the microneedle patch is shelf-stable.⁴ Additionally, this microneedle patch was used to deliver baricitinib to mice with immune-mediated AA, with a statistically comparable amount of hair regrowth as the CCL2+IL-2–coated patch.⁴ This combination of a microneedle delivery patch with already FDA-approved JAK inhibitors could result in a breakthrough treatment for patients with AA.⁴

References:

1. Alopecia Areata. National Alopecia Areata Foundation. Accessed October 21, 2024. https://www.naaf.org/alopecia-areata/
2. Żeberkiewicz M, Rudnicka L, Malejczyk J. Immunology of alopecia areata. Cent Eur J Immunol. 2020;45(3):325-333. doi:10.5114/ceji.2020.101264. Epub 2020 Nov 1.
3. Sardana K, Bathula S, Khurana A. Which is the Ideal JAK Inhibitor for alopecia areata - baricitinib, tofacitinib, ritlecitinib or ifidancitinib - Revisiting the immunomechanisms of the JAK pathway. Indian Dermatol Online J. 2023;14(4):465-474. Published 2023 Jun 28. doi:10.4103/idoj.idoj_452_22. 
4. Younis N, Puigmal N, El Kurdi A, et al. Microneedle-mediated delivery of immunomodulators restores immune privilege in hair follicles and reverses immune-mediated alopecia. Adv Mater. 2024;36(31):2312088. doi:10.1002/adma.202312088.