Researchers are focusing on an inhibitor that blocks signals. Their work could lead to new treatments for baldness.
One of the mysteries of human evolution has been why hair grows in some places on our bodies and not elsewhere.
Scientists at the University of Pennsylvania’s Perelman School of Medicine have found clues they say may help unlock that puzzle.
Using mouse skin, the researchers found the existence of a naturally occurring inhibitor that’s secreted in developing hairless skin.
The inhibitor blocks a signaling pathway, known as the WNT, that controls hair growth.
The scientists published the results of their study in the open-access online journal Cell Reports.
This breakthrough may open the door to developing products that could help restore hair where women and men want it — on their heads — and to prevent it from growing where women don’t want it, such as on their faces.
The American Academy of Dermatology reports that more than 80 million people in the United States have androgenetic alopecia, also called male pattern or female pattern baldness.
Sarah E. Millar, PhD, a professor in dermatology and director of the Penn Skin Biology and Diseases Resource-based Center, is a co-senior author of the study.
“WNT signaling is critical for the development of hair follicles,” Millar told Healthline. “Blocking it causes hairless skin and switching it on causes formation of more hair. In our study, we’ve shown the skin in hairless regions naturally produces an inhibitor that stops WNT from doing its job.”
Millar said that the pathway is switched on initially in fetal skin, where it activates genes that promote hair follicle development.
“In adult life, hair follicles go through cycles of growth, regression, rest, and regrowth,” she said. “WNT signaling is important in controlling adult hair growth as well as in the initial development of hair follicles. High levels of WNT signaling promote hair growth and when WNT signaling is blocked, the hair follicles stop growing.”
The natural inhibitor that stops WNT from doing its job is called DKK2.
This protein, found in specific embryonic and adult tissues, plays a variety of roles.
When Millar and her colleagues tested plantar (sole of the foot) skin from mice — which is like the bare underside of the human wrist — they discovered a high expression of DKK2.
When they removed DKK2 genetically, Millar said they observed hair growth in this normally hairless skin region.
“This is significant because it tells us WNT is still present in hairless regions,” Millar said. “It’s just being blocked.”
While hair follicles develop in the human fetus, the body stops producing them after birth.
That’s why hair follicles fail to regrow after severe burns or extensive, deep wounds in the skin.
“Severe wounds and burns destroy hair follicles and their associated stem cells,” Millar said. “The mechanisms that generate new hair follicles in fetal skin no longer function in adult human skin. We are investigating whether this may be due to expression of naturally occurring WNT inhibitors.”
Existing therapies for female pattern and male pattern baldness include a topical Minoxidil.
Dr. Amy McMichael is a professor and chair of the Department of Dermatology at Wake Forest Baptist Medical Center in North Carolina.
“Minoxidil is FDA-approved in all forms for men and in the 2-percent solution and 5-percent foam for women,” McMichael told Healthline. “Oral Finasteride in a 1-milligram dose is also approved for men. In terms of off-label therapies, oral Finasteride is also used for female pattern baldness as is oral Spironolactone or oral Flutamide.”
“Oral Minoxidil in low doses is another recent addition to the treatment paradigm for both men and women as an off-label treatment,” she added. “In procedural treatments, platelet-rich plasma (PRP) is making a major splash as is surgical hair restoration.”
Many of these therapies can be successful in keeping hair on the head or increasing density, especially in combination, McMichael said.
She added it’s important to be evaluated by a board-certified dermatologist to make sure that the correct therapies are offered and monitored in the appropriate way to get the best outcome.
Not all therapies are for every person, she said.
“Some of the off-label therapies can be quite expensive and medical therapy may be best,” she said. “In other cases, we don’t have markers for who will respond well and who will not.”
Dr. Nicole Rogers is a board-certified dermatologist and hair transplant surgeon who treats hair loss at Hair Restoration of the South in Louisiana.
“There is interest in regulators like DKK2 to possibly treat male- and female-pattern hair loss,” Rogers told Healthline. “However, FDA-approved treatments are currently limited to topical Minoxidil for men and women, and oral Finasteride for men only.”
“There also are a wide variety of low-level light therapy devices that have FDA clearance for hair loss. I conservatively prescribe a variety of other off-label treatments on a case-by-case basis — Spironolactone, Finasteride for women, and PRP,” she noted. “There is even interest in using oral Minoxidil for patients. Hair transplantation can also achieve a permanent and dramatic effect for many patients.”
Millar said she and her team hope their continued research will reveal new ways to improve wound healing and hair growth.
“Our research is still at a very early stage,” she said. “We still need to do a lot of work before we could think about testing potential new therapies in human patients.”