New Molecule Discovered That Strongly Stimulates Hair Growth

SCUBE3 has been found to be a potential therapeutic option for treating androgenetic alopecia.

A signaling molecule known as SCUBE3, which was discovered by researchers at the University of California, Irvine, has the potential to cure androgenetic alopecia, a prevalent type of hair loss in both women and men.

The research, which was recently published in the journal Developmental Cell, uncovered the precise mechanism by which the dermal papilla cells, specialized signal-producing fibroblasts found at the bottom of each hair follicle, encourage new development. Although the critical role dermal papilla cells play in regulating hair growth is widely established, the genetic basis of the activating chemicals involved is little understood.

“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,” says Maksim Plikus, Ph.D., UCI professor of developmental and cell biology and the study’s corresponding author. Credit: Julie Kennedy / UCI

“At different times during the hair follicle life cycle, the very same dermal papilla cells can send signals that either keep follicles dormant or trigger new hair growth,” said Maksim Plikus, Ph.D., UCI professor of developmental & cell biology and the study’s corresponding author. “We revealed that the SCUBE3 signaling molecule, which dermal papilla cells produce naturally, is the messenger used to ‘tell’ the neighboring hair stem cells to start dividing, which heralds the onset of new hair growth.”

For mice and humans to effectively develop hair, the dermal papilla cells must produce activating chemicals. Dermal papilla cells malfunction in people with androgenetic alopecia, drastically lowering the typically plentiful activating chemicals. For this study, a mouse model with excessive hair and hyperactivated dermal papilla cells was created. This model will help researchers learn more about the regulation of hair growth.

“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 & 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.

Several large human hair follicles and numerous small mouse hair follicles are shown growing in response to treatment with SCUBE3 protein. Credit: Nitish Shettigar, Plikus lab

“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.”

Reference: “Hedgehog signaling reprograms hair follicle niche fibroblasts to a hyper-activated state” by Yingzi Liu, Christian F. Guerrero-Juarez, Fei Xiao, Nitish Udupi Shettigar, Raul Ramos, Chen-Hsiang Kuan, Yuh-Charn Lin, Luis de Jesus Martinez Lomeli, Jung Min Park, Ji Won Oh, Ruiqi Liu, Sung-Jan Lin, Marco Tartaglia, Ruey-Bing Yang, Zhengquan Yu, Qing Nie, Ji Li and Maksim V. Plikus, 30 June 2022, Developmental Cell.
DOI: 10.1016/j.devcel.2022.06.005

UCI has filed a provisional patent application for the use of SCUBE3 and its related molecular compounds for hair growth stimulation. Further research will be conducted in the Plikus lab and at Amplifica Holdings Group Inc., a biotechnology company co-founded by Plikus.

The study team included health professionals and academics from UCI, San Diego, China, Japan, Korea, and Taiwan.

The study was funded by the LEO Foundation, the Chan Zuckerberg Initiative, the W.M. Keck Foundation, the National Science Foundation, the NIH/National Institutes of Health, the Simons Foundation, the National Natural Science Foundation of China, the Training Program of the Major Research Plan of the National Natural Science Foundation of China, and the Ministry of Science and Technology of Taiwan.