A team of researchers from MIT, Brigham and Women’s Hospital, and Harvard Medical School has unveiled a potential breakthrough in the treatment of alopecia areata, an autoimmune disorder that triggers hair loss across all age groups, including children.
Traditionally, patients grappling with this form of hair loss have had limited treatment options. However, the team has introduced a microneedle patch designed to be applied painlessly to the scalp. This patch dispenses drugs that help to rebalance the immune response at the affected area, effectively putting a halt to the autoimmune assault.
In experiments conducted on mice, the researchers observed that this innovative treatment not only prompted hair regrowth but also significantly reduced inflammation at the treatment site. Importantly, it achieved these effects without causing systemic immune disturbances elsewhere in the body. The researchers suggest that this approach could potentially be adapted to address other autoimmune skin conditions such as vitiligo, atopic dermatitis, and psoriasis.
Natalie Artzi, a principal research scientist at MIT’s Institute for Medical Engineering and Science, asserts that this novel approach signifies a fundamental shift. Rather than suppressing the entire immune system, the focus now lies on precisely regulating it at the point of antigen encounter to foster immune tolerance.
Artzi and Jamil R. Azzi, an associate professor at Harvard Medical School and Brigham and Women’s Hospital, lead the study, which is detailed in the journal Advanced Materials. Nour Younis and Nuria Puigmal, both postdoctoral researchers at Brigham and Women’s Hospital, serve as the lead authors of the paper.
The researchers are now laying the groundwork for establishing a company to advance the technology further. Nuria Puigmal, recently awarded a Harvard Business School Blavatnik Fellowship, is set to lead this initiative.
Alopecia areata affects over 6 million Americans and occurs when the body’s T cells target hair follicles, resulting in hair loss. The conventional treatment for most patients involves painful injections of immunosuppressant steroids into the scalp, a method often intolerable for many.
While some patients with alopecia areata and other autoimmune skin conditions receive oral immunosuppressant drugs, these medications indiscriminately suppress the immune system, leading to various adverse effects. Artzi notes that such an approach not only quells inflammation symptoms but also heightens the risk of recurrent episodes and makes individuals more susceptible to infections, cardiovascular diseases, and cancer.
The genesis of this innovative treatment can be traced back to a fortuitous encounter between Artzi and Azzi at a Washington working group meeting. Azzi, an immunologist and transplant physician, sought novel approaches to deliver drugs directly to the skin for treating skin-related ailments.
Their ensuing discussion sparked a collaboration between their respective labs, culminating in the development of a microneedle patch for drug delivery to the skin. In a previous study in 2021, they demonstrated the efficacy of such a patch in preventing rejection following skin transplants. The current study extends this approach to autoimmune skin disorders.
Azzi emphasizes the unique potential of the skin as an accessible organ for drug delivery, contrasting it with the prevalent systemic administration route. The microneedle patches utilized in this study comprise biocompatible materials, hyaluronic acid crosslinked with polyethylene glycol (PEG), commonly used in medical applications. This formulation enables drugs to penetrate the tough outer layer of the epidermis, a feat unattainable through topical creams.
Artzi explains that this polymer formulation facilitates the creation of durable needles capable of effectively piercing the skin and allows for the incorporation of various drugs. In this study, the researchers loaded the patches with a combination of cytokines IL-2 and CCL-22, which recruit regulatory T cells to dampen inflammation and educate the immune system to recognize hair follicles as non-foreign antigens.
The researchers observed a proliferation of regulatory T cells and a reduction in inflammation at the treatment site in mice treated with the patch every other day for three weeks. Hair regrowth occurred at these sites and persisted for several weeks after treatment cessation. Notably, the levels of regulatory T cells in the spleen or lymph nodes remained unchanged, indicating localized effects of the treatment.
Further experiments involving human skin grafts on mice with a humanized immune system corroborated these findings, demonstrating the patch’s ability to induce regulatory T cell proliferation and reduce inflammation.
The microneedle patches are designed to not only deliver drugs but also collect samples for monitoring treatment progress. Following patch removal, the needles swell, allowing them to absorb interstitial fluid containing biomolecules and immune cells from the skin. Researchers can then analyze these samples to assess levels of regulatory T cells and inflammation markers, potentially aiding in patient monitoring.
The researchers are now focused on refining this approach for treating alopecia and expanding its application to other autoimmune skin conditions.
