Genetic Finding Could Lead to New Targets for Treatment of Alopecia Areata, Researchers Say
By Katrina Woznicki
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Reviewed By Laura J. Martin, MD
This is one of the first studies to locate genes potentially linked to alopecia areata. What is most striking about the genes identified is that they are already associated with a number of autoimmune disorders, including type 1 diabetes and rheumatoid arthritis. Now, researchers at Columbia University Medical Center in New York suggest these genes could be targets for new alopecia areata treatments.
Genes Linked to Hair Loss
One gene in particular caught the eye of study author Angela M. Christiano, PhD, a professor of dermatology and genetics and development at Columbia, and her colleagues. Known as ULBP3, this gene is normally not present in hair follicles, but ULBP3 proteins were found in high concentrations in hair follicles affected by alopecia areata. ULBP3 attracts immune cells called cytotoxic cells. If an infection is present in the body, cytotoxic cells can help fight the infection or destroy damaged cells, but if there is no infection or damage, these immune cells end up attacking healthy tissue.
The ULBP3 proteins attract cells marked by a killer cell receptor, known as NKG2D, which is also involved in other autoimmune disorders and could potentially serve as a biomarker for alopecia areata. Two other genes were also expressed in hair follicles, while the remaining five genes were involved in immune system response.
The findings are based on the genome analysis of 1,054 people with alopecia areata and 3,278 people without the disorder and appear in the July 1 issue of Nature.
"Finding the initial genes underlying alopecia areata is a big step forward, but the nature of the genes is even more exciting," Christiano says. "There seems to be a shared mechanism among organs that express NKG2D danger signals as part of the initiating process. And since drugs are already in development that target these pathways -- because they are being tested to treat rheumatoid arthritis, type 1 diabetes, and other diseases where the NKG2D receptor is involved -- we may soon be able to test these drugs in clinical trials for alopecia areata. Finally, we have the possibility of developing drugs that specifically target the mechanism behind the disease."
New Alopecia Areata Treatments Needed
Alopecia areata was originally thought to be associated with psoriasis; however, psoriasis treatments failed to offer any benefit in treating alopecia areata. There is a 1.7% lifetime risk for alopecia areata, which can begin with a sudden whitening of hair and then losing patches of hair on the scalp. The condition may ultimately lead to complete scalp hair loss or even total body hair loss. The condition's severity varies by person and the hair does grow back in some patients. However, alopecia areata greatly affects quality of life that can be socially marginalizing, particularly for children. Current treatments range from topical foams to steroid injections.
"This research is very exciting, as alopecia areata affects a huge number of people worldwide, and there are very few treatments for it -- resulting in an enormous unmet medical need," says Vicki Kalabokes, president and CEO of the National Alopecia Areata Foundation, which funded Christiano's early pilot studies on the genetic basis of alopecia areata. "Hair loss is life-altering - sufferers, especially children, experience social stigma. It affects their quality of life and can lead to long-term psychosocial impact."
SOURCES: News release, Columbia University.
Petukhova, L. Nature, July 1, 2010; vol 466.
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