UCLA Researchers Make Hair Growth Stem Cell Breakthrough

Research into what causes hair loss seems to be at an all time high. With an ageing and increasingly stressed global population, where the problem of genetic and/or lifestyle-related hair thinning is growing apace, finding new methods of preventing baldness has become a stated ambition of many pharmaceutical companies.

Exploring the biological mechanisms that contribute to different hair loss conditions often opens up new explorative avenues for teams involved in the development of new treatments.

Now, new research from the University of California, Los Angeles (UCLA) unveils what appears to be a critical breakthrough in stimulating hair growth.

Activating stem cells to stimulate hair growth

The American team's findings, published in the Nature Cell Biology journal, explain how the team investigated how hair follicle stem cells could be stimulated in order to produce hair growth.

Heather Christofk and William Lowry led the team from UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. Together they made the breakthrough discovery that hair follicles have a unique stem cell metabolism.

The team's study found that stem cells in hair follicles are usually dormant but, when a new hair growth cycle begins, they quickly become active. Their inactive state is known as "quiescence" and there are many factors involved in regulating this period. Hair loss can occur when this regulation fails in some way and the follicles fail to switch into an active state.

The follicle stem cells process glucose, sourced from the bloodstream, turning it into something called a 'pyruvate metabolites'.  These small, organic molecules are necessary for creating energy when the pryurvate is sent to the mitochondria - essentially the power source of cells. But, if the pryurvate is instead converted into a different metabolte called lactate, this can result in increased hair growth activity.

By testing this theory on mice, UCLA researchers, working with the University of Utah's Rutter laboratory, managed to successfully boost lactate production. In turn, this caused an increase in the hair follicle's stem cell activation and a resultant speeding up of the hair growth cycle in the test mice.

"Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate and if that would activate the cells and grow hair more quickly," said Christofk.

Lowry added, "Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect."

Treating hair loss via the JAK-Stat pathway

According to the UCLA team's findings, two separate types of experimental drugs were tested - also on mice - in order to encourage increased lactate production. The first of these was RCGD423, a drug that activates the JAK-STAT pathway, leading to inflated levels of lactate.

The JAK (Janus tyrosine Kinase) -STAT (Signal Transducer and Activator of Transcription), or 'JAK-STAT' pathway has come under increased scrutiny from hair loss researchers recently. It was discovered that manipulating this cell-signalling channel, which transmits outside information to the heart of cells, could extend the 'anagen' active growth phase of the hair's natural cycle.

Since then researchers have been trying to develop JAK inhibitor drugs to treat a number of hair loss conditions. These have mostly concentrated on the most severe forms of the autoimmune disorder, Alopecia Areata - Alopecia Totalis and Alopecia Universalis which both cause total baldness and, unlike moderate Alopecia Areata, are currently untreatable.

In addition to RCGD423, a second drug called UK5099 was also developed. This showed during the UCLA trial that it could force the follicle stem cells into lactate production by blocking pyruvate from the mitochondria.

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Predoctoral trainee Aimee Flores, who was named as a study author and works alongside Dr. Lowry, explained, "Through this study, we gained a lot of interesting insight into new ways to activate stem cells. The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think we've only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; I'm looking forward to the potential application of these new findings for hair loss and beyond."

US patent applications in relation to promoting hair growth have been filed for both drugs by the UCLA Technology Development Group on behalf of UC Regents.

Exciting as these breakthroughs appear, it can take many years for new medicines to pass the necessary safety, tolerability and efficacy tests in order to then be released for prescription. These trials are in the pre-clinical stage, which is extremely early on in the research and development process. Other JAK inhibitor treatments for Alopecia Areata, such as baricitinib, are currently further along and are estimating a 2020/2021 release. Pfizer, the big pharma giant which produces Xeljanz (tofacitinib citrate) - another potential Alopecia Universalis treatment - is also entering the later stages of testing with new JAK inhibitors for hair loss.

It is understood that once these drugs have managed to be successfully released as alternative alopecia areata treatments, they will be redeveloped for use on genetic hair loss - Male Pattern Baldness and, for women, Female Pattern Hair Loss. There are, of course, already clinically proven hair loss treatments that help many, many men and women prevent shedding and promote hair growth, worldwide. Given this inherited form of alopecia causes thinning hair that progressively worsens over time, it can be a relief when people discover these options already exist so there's no need to wait years to start treatment!