Alopecia areata is an autoimmune condition that causes hair loss and can be suffered by people of all ages, including children. For most people affected by this type of hair loss, there is no effective treatment, but now researchers from MIT (Massachusetts Institute of Technology), Brigham and Women’s Hospital, and Harvard Medical School have developed a new therapy that could solve this problem.
The new treatment consists of a microneedle patch that can be applied painlessly to the scalp and releases medications that help rebalance the immune response in the area, stopping the autoimmune attack. In a study with mice, researchers found that this treatment allowed hair to regrow and dramatically reduced inflammation at the treatment site, while preventing systemic immune effects elsewhere in the body.
This strategy could also be adapted to treat other autoimmune skin diseases such as vitiligo, atopic dermatitis and psoriasis, the researchers say. Artzi and Jamil R. Azzi, associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, are senior authors of the new study, which has been published in the journal Advanced Materials.
“This innovative approach marks a paradigm shift. Instead of suppressing the immune system, we are now focusing on regulating it precisely at the site of antigen encounter to generate immune tolerance,” says Natalie Artzi, senior research scientist at the Institute of Engineering and Medical Sciences from MIT, associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, and associate faculty member of the Wyss Institute at Harvard University.
A potential therapy against alopecia and other skin diseases
Alopecia areata occurs when the body’s own T cells attack the hair follicles, resulting in hair loss. The only treatment available to most patients (scalp injections of immunosuppressive steroids) is painful and is often not tolerated by patients.
Some patients with alopecia areata and other autoimmune skin diseases may also be treated with immunosuppressants, medications that are administered orally, but which lead to widespread suppression of the immune system, which can have adverse side effects. “This approach silences the entire immune system, offering relief from inflammation symptoms, but causing frequent recurrences. Additionally, it increases susceptibility to infections, cardiovascular diseases and cancer,” says Artzi.
A few years ago, at a task force meeting in Washington, Artzi was sitting next to Azzi, an immunologist and transplant doctor who was looking for new ways to deliver drugs directly to the skin to treat skin-related diseases. Their conversation led to a new collaboration, and the two labs joined forces to work on a microneedle patch that would deliver drugs to the skin. In 2021, they reported that such a patch can be used to prevent rejection after a skin transplant. In the new study, they began applying this approach to autoimmune skin disorders.
“The skin is the only organ in our body that we can see and touch, and yet when it comes to drug delivery to the skin, we went back to systemic delivery. We saw great potential in using the microneedle patch to reprogram the immune system locally,” says Azzi.
In mice treated with this patch every two days for three weeks, hair was able to grow again and this growth was maintained for several weeks after finishing the treatment.
The microneedle patches used in this study are made of hyaluronic acid cross-linked with polyethylene glycol. (PEG), both biocompatible and commonly used in medical applications. With this method of administration, medications can pass through the tough outer layer of the epidermis, which cannot be penetrated by creams applied to the skin. “This polymer formulation allows us to create highly durable needles capable of effectively penetrating the skin, plus it gives us the flexibility to incorporate any desired medication,” says Artzi.
For this study, the researchers loaded the patches with a combination of the cytokines IL-2 and CCL-. 22. Together, these immune molecules help recruit regulatory T cells, which proliferate and help reduce inflammation. These cells also help the immune system recognize that the hair follicles are not foreign antigens, so it stops attacking them.
The researchers found that mice treated with this patch every other day for three weeks had many more regulatory T cells present at the site, along with a reduction in inflammation. Hair was able to grow back at those sites and this growth was maintained for several weeks after completing the treatment. In these mice there were no changes in the levels of regulatory T cells in the spleen or lymph nodes, suggesting that the treatment affected only the site where the patch was applied.
In another series of experiments, the researchers grafted human skin onto mice with a humanized immune system. In these mice, microneedle treatment also induced the proliferation of regulatory T cells and a reduction in inflammation. They designed the microneedle patches so that, after releasing their drug payload, they could also collect samples that could be used to monitor treatment progress. Hyaluronic acid causes the needles to swell about 10 times after entering the skin, allowing them to absorb interstitial fluid containing biomolecules and immune cells from the skin.
After removing the patch, researchers can analyze samples to measure levels of regulatory T cells and markers of inflammation. This could be valuable in monitoring future patients who may undergo this treatment. The researchers now plan to further develop this approach to treating alopecia and expand it to other autoimmune skin diseases.
