Using a hydrogel microneedle system to deliver immune-modulating therapy directly to areas of alopecia-areata-related hair loss has demonstrated marked and lasting increases in hair regrowth in models of the disease.
The findings were published in Advanced Materials.
In a press release from Brigham and Women's Hospital, the investigators note that in autoimmune conditions such as alopecia areata, immune T cells mistakenly attack hair follicles, and the regulatory T cells (Tregs) that are supposed to downregulate other T cells also inadequately perform their function. Current immunosuppressants used to treat alopecia areata target both T cells and Tregs, the authors write, which fail to address the core issue and increase the risk of disease recurrence once treatment stops. Moreover, systemic immune therapy suppresses the entire immune system, leaving patients vulnerable to infections and malignancies.
For this study, the researchers aimed to restore well-controlled immune activity locally by increasing levels of Tregs directly at sites of hair loss. They used a microneedle patch to deliver medications across the tough outer layer of skin and avoid stimulating pain receptors.
“Our strategy tackles two major challenges in treating autoimmune skin diseases,” said co-corresponding author Natalie Artzi, PhD, of the Brigham’s Engineering in Medicine Division in the Department of Medicine, in the release. “Our patches enable local delivery of biologics, which, instead of suppressing the immune system, promote regulatory T cells in the skin. This restores immune balance and resolves the T cell attack on hair follicles, offering a potential long-term solution without compromising the immune system's ability to defend against infections and malignancies.”
“When it comes to autoimmune-mediated skin diseases, where we have direct access to the skin, we must surpass the use of systemic immunosuppressants that shut down the entire immune system,” said co-corresponding author Jamil Azzi, MD, PhD, an immunologist in the Brigham’s Renal Division in the Department of Medicine. “While topical therapy often fails to penetrate the skin's outer layer, our patches improve the local delivery of biologics to the deeper layers of diseased skin and reprogram the immune system to generate tolerance at the site of antigen encounter.”
The researchers observed that in AA tissues, there were changes in the STAT-5/Interleukin-2 (IL-2) signalling pathway. Therefore, for this study, they loaded a microneedle patch with IL-2, which promotes Treg proliferation, and CCL22, which the researchers had previously shown attracts and expands the presence of Tregs in a specific area. The patches were applied to murine models of AA 10 times over the course of three weeks, with more than eight weeks of observation. Investigators observed hair regrowth as early as three weeks after the initiation of treatment. The researchers also tested microneedle patches loaded with baricitinib, a therapy approved for severe AA, but found that Treg recruitment was inferior to that associated with the IL-2/CCL22 patch.
They also found the microneedle patch had good shelf-life stability, improving the prospects of its clinical translation. While the therapy is not ready for clinical use, the researchers are pursuing further development and testing. Additionally, they are exploring the possibility of applying their approach to other immune-mediated skin diseases, such as vitiligo and psoriasis.
“Microneedles offer a promising avenue for targeted and localized delivery of therapeutics to the skin,” said Dr. Artzi. “Their ability to precisely administer drugs directly to the affected area of the skin enables more effective modulation of the immune response while minimizing systemic side effects. This targeted approach holds great potential for improving treatment outcomes and reducing the burden of autoimmune and immune-mediated diseases on patients’ lives.”
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