Odor-sensing protein spurs hair growth

If the cure to baldness has a scent, it may smell like sandalwood. Researchers have discovered a receptor in hair follicles that activates in response to a sandalwood-scented molecule, initiating a biological cascade promoting hair growth (Nat. Commun. 2018, DOI: 10.1038/s41467-018-05973-0). The finding may lead to a novel treatment for hair loss.

Originally identified in the nose, olfactory receptors capture odorant molecules, generating downstream cellular activity that produces the sense of smell. Olfactory receptors were subsequently discovered, curiously, in other parts of the body, such as the gut, kidneys, and skin. This prompted the big question: What are olfactory receptors doing in organs without nostrils? “Nobody has a very convincing answer yet,” says Ralf Paus of the University of Miami, Florida. “They are labeled as smell receptors, but they are actually chemoreceptors. Evolutionarily, these olfactory receptors are much older than the development of a brain. The brain hijacked these receptors for a complex system of smell.”

In prior work, Paus and colleagues studied an olfactory receptor, OR2AT4, found in skin cells. They observed an increase in skin cell proliferation and wound healing after OR2AT4 bound to Sandalore (shown), a trademarked synthetic sandalwood odorant used in many perfumes and products. Wound healing and hair growth are connected, says Paus, which gave him the idea to look for OR2AT4 in hair follicles.

Using methods including immunofluorescence microscopy, the researchers determined that hair follicles indeed express OR2AT4 during the part of their cycle associated with hair growth. When the researchers then treated cultured human hair follicles with Sandalore for six days, they saw an increase in the expression of OR2AT4 and a prolongation of the hair follicles’ growth phase. “This is clinically relevant,” says Paus, “To have less hair loss, you want to keep hair in its growth phase. It’s when the growth phase ends that hair is lost,” says Paus.

To figure out what happens inside the hair follicles after OR2AT4 snags a Sandalore molecule to keep the hair growth going, Paus looked at two key regulators of the hair cycle, IGF-1, which promotes the growth phase, and TGF-β2, which favors hair loss. The Sandalore-treated hair follicles had around a 25% increase in IGF-1 expression and a 25% decrease in TGF-β2 expression. Furthermore, blocking IGF-1 with an antibody prevented Sandalore from prolonging the hair growth phase, supporting the key role of IGF-1.

People with hair loss concerns may not have long to wait before a Sandalore-based treatment is developed. “Sandalore is already offered as a cosmetic product in Italy by the company that has cosponsored the current study,” says Paus. A large clinical trial of Sandalore’s effect on hair loss in female volunteers with increased hair shedding is currently ongoing with results expected in early 2019. “This treatment could potentially work to prevent most types of hair loss,” says Paus. “There is even a chance that this might be able to bring the hair back.”

“Olfactory receptors are similar to other receptors, so you can target them pharmacologically,” says Johannes Reisert of the Monell Chemical Senses Center. “This is a solid idea to combat hair loss.” Though he adds that more research may be needed to figure out the effective dose or, if necessary, develop a more potent treatment. “I don’t know if you would want a shampoo with a huge amount of sandalwood. You might smell like sandalwood for five days.”