New treatment may reverse hair loss caused by autoimmune skin disease

Microneedle patches that deliver immunomodulatory molecules teach T cells not to attack hair follicles, thereby supporting hair regrowth.

New treatment may reverse hair loss caused by  autoimmune skin disease

Researchers at the Massachusetts Institute of Technology, Brigham and Women's Hospital, and Harvard Medical School have discovered a potential new treatment for alopecia areata, an autoimmune disease that causes hair loss and affects people of all ages, including children. was developed.

Most patients with this type of hair loss have no effective treatment. Researchers have developed a microneedle patch that can be applied painlessly to the scalp and stops autoimmune attacks by releasing drugs that help rebalance the immune response in the area.

In a study in mice, researchers found that the treatment allowed hair to regrow and dramatically reduced inflammation in the treated area, while avoiding systemic immune effects in other parts of the body. I discovered that. The researchers say this strategy could also be applied to treat other autoimmune skin diseases such as vitiligo, atopic dermatitis, and psoriasis. "This innovative approach represents a paradigm shift. Rather than suppressing the immune system, we now focus on precisely controlling the immune system at the site of antigen encounter to create immune tolerance." ,” said Natalie Artzi, a senior researcher at the Institute of Biomedical Engineering. Scientist at MIT, Associate Professor of Medicine at Harvard Medical School and Brigham and Women's Hospital, and Adjunct Instructor at Harvard's Wyss Institute.

Artzi and his colleague Jamil R. Azzi, associate professor of medicine at Harvard Medical School and Brigham and Women's Hospital, are senior authors of the new study, published in the journal Advanced Materials. Nour Younis, a postdoctoral fellow at Brigham and Women, and Nuria Puigmal, a postdoctoral fellow at Brigham and Women and a former MIT research partner, are the paper's lead authors. The researchers are now working to form a company to further develop the technology, led by Puigmal, who recently received a Blavatnik Fellowship from Harvard Business School.

Direct delivery

Alopecia areata, which affects more than 6 million Americans, occurs when the body's own T cells attack the hair follicles, causing hair loss. The only treatment available to most patients is an injection of immunosuppressive steroids into the scalp, which is painful and often not tolerated by patients.

Some patients with alopecia areata and other autoimmune skin diseases can also be treated with oral immunosuppressants, but these drugs cause widespread immune system suppression and can have harmful side effects. There is a gender.

"This approach silences the entire immune system and reduces inflammatory symptoms, but leads to frequent relapses. Additionally, it increases susceptibility to infections, cardiovascular disease, and cancer," says Artzi. . A few years ago, Mr. Artzi happened to be sitting next to Azzi at a working group meeting in Washington (seating was arranged alphabetically). He was an immunologist and transplant doctor who was looking for new ways to deliver drugs directly to the skin to treat it. disease.

Their conversation led to a new collaboration, and the two labs joined forces to develop a microneedle patch that delivers drugs to the skin. In 2021, they reported that such patches could be used to prevent rejection after skin grafts. New research has begun to apply this approach to autoimmune skin diseases.

"The skin is the only organ in our bodies that we can see and feel, yet we still rely on systemic administration to deliver drugs to the skin." “We saw great potential in locally reprogramming the immune system using microneedle patches,” Azzi says.

The microneedle patches used in this study are made of hyaluronic acid cross-linked with polyethylene glycol (PEG), both of which are biocompatible and commonly used in medical applications. This method of administration allows the drug to penetrate the hard outer layer of the epidermis, which creams applied to the skin cannot penetrate.

"This polymer formulation allows us to create extremely durable needles that can effectively penetrate the skin, while also giving us the flexibility to incorporate the drug we need," he says. . For this study, the researchers loaded the patch with a combination of the cytokines IL-2 and CCL-22. Together, these immune molecules help recruit regulatory T cells, which proliferate and help control inflammation. These cells also help the immune system recognize that the hair follicle is not a foreign antigen and stop attacking the hair follicle.

Hair regrowth

The researchers found that when mice were treated with the patch every other day for three weeks, there were more regulatory T cells in the area and less inflammation. Hair was able to regrow in these areas, and this growth continued for several weeks after treatment ended. 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 patched area.

In another series of experiments, researchers transplanted human skin into mice with humanized immune systems. In these mice, microneedle treatment also induced regulatory T cell proliferation and reduced inflammation. The researchers designed the microneedle patch so that after releasing the drug payload, it could collect a sample that could be used to monitor the progress of the treatment. The hyaluronic acid causes the needle to expand approximately 10 times after it penetrates the skin, allowing it to absorb interstitial fluid containing biomolecules and immune cells from the skin.

After removing the patch, researchers can analyze the sample to measure the amount of regulatory T cells and inflammatory markers. This may prove useful in monitoring future patients who may receive this treatment.

The researchers now plan to further develop this approach to treat alopecia and extend it to other autoimmune skin diseases. This research was funded by Ignite Fund and Shark Tank Fund awards from the Brigham and Women's Hospital School of Medicine.