A team led by University of California, Irvine researchers may have taken a step closer to treating baldness.
Researchers have found a signaling molecule called SCUBE3 that potently stimulates hair growth and may offer a therapeutic treatment for androgenetic alopecia, the most common form of hair loss in men and a malady that also affects women.
The study, published online on June 30 in Developmental Cell, determined the precise mechanism by which the dermal papilla cells—specialized signal-making fibroblasts at the bottom of each hair follicle—promote new growth.
In the U.S., about 50 million males suffer from hair loss while another 30 million females do as well, particularly older women, said Dr. Maksim Plikus, a UCI professor of developmental and cell biology and the study’s corresponding author.
“It’s a big population out there,” he told the Business Journal. “When it comes to hair loss, this is an unmet clinical need. There’s a lot of opportunity to innovate in this field and for new medicine.”
He said the current market doesn’t have an effective treatment for hair loss. Hair transplantation has a conundrum in that there usually are not enough healthy hair follicles to be planted in the bald areas, he said.
A head typically has 500,000 hair follicles, each of which could be compared to a 3D printer that respectively reprints a strand of hair, he said.
When baldness occurs, it’s because a follicle doesn’t have an activator telling it to print hair. Plikus’ research is getting closer to identifying those activators, he said.
“If one could identify what those activating molecules are, they should kickstart dormant follicles to grow,” he said. “It’s been challenging because such molecules are elusive.”
Plikus’ study showed that SCUBE3 is the messenger used to tell the neighboring hair stem cells to start dividing, which heralds the onset of new hair growth.
“We are pursuing a molecule that should restart hair growth,” he said.
Plikus has long been fascinated by skin. A winner of awards from Pew and the LEO Foundation, he’s developing new ways to help the human body regenerate skin—without scars—by exploring the mechanisms behind tissue repair and stem cell control.
Plikus’ work was supported by grants from entities including the LEO Foundation, the Chan Zuckerberg Initiative, the W.M. Keck Foundation, the National Science Foundation, the Simons Foundation, and the National Institute of Health.
The study team included health professionals and academics from UCI, San Diego, China, Japan, Korea and Taiwan.
UCI has filed a provisional patent application on the use of SCUBE3 and its related molecular compounds for hair growth stimulation.
Further research will be conducted in Plikus’ UCI lab and at San Diego-based Amplifica Holdings Group Inc., a biotechnology company co-founded by Plikus and joined by Wajdie Ahmad, who worked at Allergan and later co-founded neurotoxin firm Bonti Inc., which Allergan bought in 2018 for $195 million.
Of Mice and Men
A mouse model with hyperactivated dermal papilla cells and excessive hair, which will facilitate more discoveries about hair growth regulation, was developed for this research.
“Studying this mouse model permitted us to identify SCUBE3 as the previously unknown signaling molecule that can drive excessive hair growth,” said co-first author Yingzi Liu, a UCI postdoctoral researcher in developmental and cell biology.
Further tests validated that SCUBE3 activates hair growth in human follicles. Researchers microinjected SCUBE3 into mouse skin in which human scalp follicles had been transplanted, inducing new growth in both the dormant human and surrounding mouse follicles.
“These experiments provide proof-of-principle data that SCUBE3 or derived molecules can be a promising therapeutic for hair loss,” said co-first author Christian Guerrero-Juarez, a UCI postdoctoral researcher in mathematics.
Currently, there are two medications on the market—finasteride and minoxidil—that are approved by the Food and Drug Administration for androgenetic alopecia. Finasteride is only approved for use in men. Both drugs are not universally effective and need to be taken daily to maintain their clinical effect.
“There is a strong need for new, effective hair loss medicines, and naturally occurring compounds that are normally used by the dermal papilla cells present ideal next-generation candidates for treatment,” Plikus said. “Our test in the human hair transplant model validates the preclinical potential of SCUBE3.”