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GONE TODAY, HAIR TOMORROW: Topical Application of JAK Inhibitors Awakens Resting Hair Follicles; Treatment May Prove Effective in Restoring Hair Growth in Multiple Forms of Hair Loss, But Not Yet Shown

Inhibiting a family of enzymes inside hair follicles that are suspended in a resting state restores hair growth, a new study from researchers at Columbia University Medical Center (CUMC) has found. The research was published online on October 23, 2015 in an open-access article in Science Advances. The article is titled “Pharmacologic Inhibition of JAK-STAT Signaling Promotes Hair Growth.” In experiments carried out with mouse and human hair follicles, Angela M. Christiano (photo), Ph.D., and CUMC colleagues found that drugs that inhibit the Janus kinase (JAK) family of enzymes promote rapid and robust hair growth when applied direcly to the skin. [Note that the press release, for which a link is provided below, includes a video of Dr. Christiano explaining her group's new findings.] The study raises the possibility that drugs known as JAK inhibitors could be used to restore hair growth in multiple forms of hair loss such as that induced by male-pattern baldness, and additional types that occur when hair follicles are trapped in a resting state. Two JAK inhibitors have been approved by the U.S. Food and Drug Administration (FDA) for other indications. One is approved for the treatment of blood diseases (ruxolitinib) and the other for rheumatoid arthritis (tofacitinib). Both JAK inhibitors are currently being tested in clinical trials for the treatment of plaque psoriasis and alopecia areata, an autoimmune disease that causes hair loss. "What we've found is promising, though we haven't yet shown it is effective for male-pattern baldness," said Dr. Christiano. "More work needs to be done to test formulations of JAK inhibitors specially made for the scalp to determine whether they can induce hair growth in humans." Dr. Christiano and her colleagues serendipitously discovered the effect of JAK inhibitors on hair follicles when they were studying a type of hair loss known as alopecia areata, caused by an autoimmune attack on the hair follicles. Dr. Christiano and colleagues reported last year that JAK inhibitors shut off the signal that provokes the autoimmune attack, and that oral forms of the drug restore hair growth in some people with the disorder. In the course of those experiments, Dr. Christiano noticed that mice grew more hair when the drug was applied topically to the skin than when given internally. This suggested JAK inhibitors might have a direct effect on the hair follicles, in addition to inhibiting the immune attack. When the researchers looked more closely at normal mouse hair follicles, they found that JAK inhibitors rapidly awakened resting follicles out of dormancy. Hair follicles do not produce hair constantly but rather by cycling between resting and growing phases.

JAK inhibitors trigger the follicles' normal reawakening process, the researchers found. Mice treated for five days with one of two JAK inhibitors sprouted new hair within 10 days, greatly accelerating the hair follicle growth phase. No hair grew on untreated control mice in the same time period.

"There are very few compounds that can push hair follicles into their growth cycle so quickly," said Dr. Christiano.

"Some topical agents induce tufts of hair here and there after a few weeks, but very few have such a potent and rapid-acting effect."

The drugs also produce longer hair from human hair follicles grown in culture and on skin grafted onto mice.

It's likely that the drugs that are so effective in enhancing hair growth in the mice could affect the same pathways in human follicles, suggesting they could induce new hair growth and extend the growth of existing hairs in humans.

It remains to be seen if JAK inhibitors can reawaken hair follicles that have been suspended in a resting state because of androgenetic alopecia (which causes male-pattern and female-pattern baldness) or other forms of hair loss.

So far, all the experiments have been conducted in normal mice and human follicles. Experiments to address hair follicles affected by hair loss disorders are under way.

In addition to Dr. Christiano, other CUMC authors on this new article are Sivan Harel, Claire Higgins (now at Imperial College London) Jane E. Cerise, Zhenpeng Dai, James C. Chen, and Raphael Clynes (now at Bristol-Myers Squib).

Columbia University has filed patent applications relating to the discoveries reported in this paper, which are being commercialized through Vixen Pharmaceuticals, Inc., of which Dr. Christiano is a founder. The other authors report no conflict of interest.

[Press release] [Science Advances article]

[U.S. News & World Report article] [Daily Mail article] [Medical News Today article] [Medical Xpress article] [NBC News article]