Hair Loss: Hair Restoration And New Drugs

26 Sep

Alopecia areata – an autoimmune skin disease that causes patchy hair loss on the scalp, face, and body – affects as many as 6.8 million people in the United States. Researchers from Columbia University Medical Center have identified a promising therapy for the disease that stimulated hair regrowth by 92 percent.

[Alopecia sign with question marks]
Researchers have found that JAK inhibitors may help people with alopecia areata regrow their hair.

With all forms of alopecia area, the body’s immune system attacks healthy hair follicles, which causes them to become smaller and decrease in production to the point where hair growth may stop altogether.

For people who have less than 50 percent hair loss, current treatment options work to disrupt or distract the immune attack and stimulate the hair follicle. For people who experience more than 50 percent hair loss, there are oral and injectable medications available. However, these treatments are not successful for everyone.

Columbia University Medical Center (CUMC) researchers conducted an open-label clinical trial – whereby both researchers and participants knew what treatment was administered – of 12 people with alopecia areata.

The findings, published in the Journal of Clinical Investigation/Insight, were released alongside a separate study from Stanford University and Yale University that tested a similar drug.

JAK inhibitors could stimulate hair growth

Alopecia areata is the second most common form of hair loss that occurs at any age and affects both men and women equally.

While there is currently no treatment capable of completely restoring hair, CUMC investigators have shown that topical and oral drugs that inhibit the Janus kinase (JAK) family of enzymes, known as JAK inhibitors, could potentially fill the role of stimulating hair regrowth.

“Although our study was small, it provides crucial evidence that JAK inhibitors may constitute the first effective treatment for people with alopecia areata,” says Dr. Julian Mackay-Wiggan, associate professor of dermatology and director of the Clinical Research Unit in the Department of Dermatology at CUMC, and a dermatologist at NewYork-Presbyterian/Columbia.

“This is encouraging news for patients who are coping with the physical and emotional effects of this disfiguring autoimmune disease,” she adds.

Previous research by the team revealed specific immune cells and dominant inflammatory signaling pathways that are responsible for attacking the hair follicle in people with alopecia areata, resulting in the follicle entering a dormant state.

Later studies of mouse and human hair follicles showed that JAK inhibitors reawaken these dormant follicles by blocking inflammatory signaling.

Three quarters of participants exhibited 50 percent more hair regrowth

The U.S. Food and Drug Administration (FDA) have already approved two JAK inhibitors: a medication used to treat bone marrow malignancies called ruxolitinib, which was the focus of the CUMC research, and a treatment for rheumatoid arthritis called tofacitinib that the Stanford/Yale study explored.

“These disorders are both characterized by dysregulated signaling pathways, similar to alopecia areata, which is dominated by the interferon signaling pathway. Even though the diseases are very different, this common feature gave us the initial idea to test JAK inhibitors in people with alopecia,” says Dr. Raphael Clynes, Ph.D., associate professor of dermatology at CUMC.

The researchers tested their hypothesis by enrolling 12 people with moderate to severe alopecia with more than 30 percent hair loss. Participants were administered 20 milligrams of oral ruxolitinib twice a day for 3-6 months. Follow-up took place over a further 3 months to assess the permanence of treatment response.

Results showed that nine of the patients – 75 percent – presented 50 percent or more hair regrowth. By the end of the treatment period, 77 percent of participants who responded to ruxolitinib therapy achieved more than 95 percent hair regrowth.

In the follow-up period, one third of people who had responded to the treatment proceeded to experience significant hair loss, although not to the degree of before treatment.

Inflammatory indicators may identify responders, nonresponders

Skin biopsies were performed before, during, and after treatment. In responders, the biopsies showed a reduction in levels of interferon signaling and cytotoxic T lymphocytes, which are indicators of inflammatory response. They also had increased levels of hair keratins, which are proteins that indicate hair growth. These levels are similar to those seen in people without alopecia areata.

People with alopecia areata who did not respond to treatment had lower levels of inflammatory signatures in biopsy results before treatment began, which may indicate that scientists could potentially distinguish between people who will and will not respond to treatment.

“We are very excited about the use of biomarkers to follow the response of patients to this treatment,” says Angela M. Christiano, Ph.D., the Richard and Mildred Rhodebeck professor of dermatology and professor of genetics and development at CUMC. “This will allow us to so monitor improvements in their gene expression signatures even before hair growth appears.”

“Our findings suggest that initial treatment induces a high rate of disease remissions in patients with moderate to severe alopecia areata, but maintenance therapy may be needed.”

Dr. Julian Mackay-Wiggan

“While larger, randomized trials are needed to confirm the safety and efficacy of ruxolitinib in people with moderate to severe alopecia areata, our initial results are very encouraging,” Mackay-Wiggan adds.

The Stanford/Yale study also showed a positive response to the JAK inhibitor tofacitinib. “Together, the two studies show that we’re on the right track,” says Dr. Christiano, a co-author of the tofacitinib paper.

Future research by the CUMC team will focus on testing JAK inhibitors in conditions such as vitiligo, scarring alopecia, and male pattern baldness. “We expect JAK inhibitors to have widespread utility across many forms of hair loss based on their mechanism of action in both the hair follicle and immune cells,” concludes Dr. Christiano.

Watch a video explaining the findings of the CUMC research:

Learn about the causes, symptoms, and treatments for alopecia areata.

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