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Androgenetic alopecia, or more often baldness, is associated with genetic and hormonal factors and occurs mainly after 50 years. But more and more young people are suffering from it at an early age. The treatment market is lucrative, but its effectiveness is low. Researchers have recently developed a new injectable treatment that can re-grow dormant follicles. Trials in mice are promising, and its use in humans is already under consideration.
In men, the prevalence of androgenetic alopecia, or male pattern baldness, becomes more common with age. It is estimated that it affects 20% of 20-year-old men, 30% of 30-year-old men, 40% of 40-year-old men, etc. It occurs less often in women: only one woman in five at the age of 40 and one woman in four at the age of 60.
You should be aware that this is a hereditary disease caused by a genetically determined sensitivity to the effects of dihydrotestosterone (DHT) in certain areas of the scalp. DHT is believed to shorten the growth phase of the hair cycle, which typically lasts 3-6 years, to a few months or weeks. This is followed by miniaturization of the follicles and gradually produces fewer and finer hairs. The production of DHT is regulated by the enzyme 5-alpha reductase.
Several genes are involved, which explains the age of onset and progression. Predisposition genes are inherited from both mother and father. Women are less susceptible to this disease, as they have lower levels of male hormones. However, some women experience male-pattern hair loss due to excessive androgen levels as well as a genetic predisposition.
More and more young people are being consulted about premature hair loss, often associated with the stress of current life, with infectious factors, as well as with an unbalanced diet. Baldness is a social problem for many people, highlighting the apparent lack of effective treatments.
Recently, an international team of researchers led by the University of California, Irvine (UCI) discovered a signaling pathway that stimulates hair growth. This may suggest a gene therapy for androgenetic alopecia. The study is published in the journal Developmental Cell.
Hair stimulation and growth in mice
Specifically, the team identified the precise mechanism by which dermal papilla cells — signaling-specialized fibroblasts located at the bottom of each hair follicle — promote new growth. Although dermal papilla cells are known to play a central role in the control of hair growth, the genetic basis of the activating molecules involved is poorly understood.
Maxim Plikus, PhD, UCI Professor of Developmental and Cellular Biology and corresponding study author, said in a statement: “At different times in the hair follicle life cycle, the same dermal papilla cells can send signals that keep the follicles in a dormant state. . or cause new hair to grow.”
Indeed, the production of activator molecules by dermal papilla cells is essential for efficient hair growth in mice and humans. In people with androgenetic alopecia, the cells in the dermal papillae malfunction, resulting in a dramatic decrease in the normally large number of activating molecules.
For this study, as in other studies of hairiness using genetic reprogramming, a mouse model with hyperactivated dermal papilla cells and excessive hairiness was developed, which will facilitate future discoveries in the field of regulation of hair growth. Then, based on RNA sequencing, the researchers identified the signaling molecule SCUBE3, which dermal papilla cells naturally produce. The authors noted that in “normal” mouse skin, SCUBE3 is expressed only in growing dermal papillae, but not in resting follicles.
Graphic summarizing the principle of the follicle growth stimulation study after SCUBE3 injection. © Yingzi Liu et al., 2022 (modified by Laurie Henry for Trust My Science)
Yingji Liu, co-author and UCI postdoctoral fellow in developmental and cell biology, explains: “Studying this mouse model allowed us to identify SCUBE3 as a previously unknown signaling molecule that can lead to excessive hair growth. In other words, this molecule is a messenger that induces the division of ciliated stem cells, marking a new phase of hair growth.
Hope for abundant hair in men
The researchers subsequently tested the molecule in humans to see if the mouse effects were tolerable. Indeed, they microinjected SCUBE3 into the skin of mice transplanted with human scalp follicles, inducing new growth in both dormant human follicles and surrounding mouse follicles. These tests confirmed that SCUBE3 indeed activates hair growth in human follicles.
Cristian Guerrero-Juarez, co-author and UCI Mathematics Fellow, says: “These experiments provide supporting evidence that SCUBE3 or derivative molecules may be a promising treatment for hair loss.”
There are currently two drugs on the market, finasteride and minoxidil, that are approved by the Food and Drug Administration for the treatment of androgenetic alopecia. Finasteride is only approved for men. Both drugs are not universally effective and must be taken daily to maintain their clinical effect.
Maxim Plikus says: “There is an urgent need for new effective anti-hair loss drugs, and natural compounds that are commonly used by dermal papilla cells are ideal candidates for a new generation of treatments. Our test in a human hair transplant model confirms the preclinical potential of SCUBE3.”
Finally, UCI has filed a provisional patent application for the use of SCUBE3 and related molecular compounds to stimulate hair growth. What’s more, for Wired magazine, the latter clarifies that SCUBE3 will be administered – the dose in micrograms – several times a year to a depth of less than a millimeter, so the procedure will be short (less than 20 minutes) and almost painless. Further research will be carried out at the Plikus laboratory and at Amplifica Holdings Group Inc., a biotechnology company co-founded by Plikus.