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UCLA Researchers Focus on Metabolites as Key Play in Hair Loss and Hair Growth

In what is becoming a regular occurrence, scientists are again celebrating the possibility that new research may lead to the development of medical treatments that promote hair growth. Researchers at UCLA have published their findings in the journal Nature Cell Biology, describing their discovery of a new way to activate the stem cells in hair follicles to make hair grow.

Scientists Heather Christofk and William Lowry of Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, spearheaded the study.

Hair follicle stem cells are present in the skin and produce hair throughout a person’s lifetime. While they are normally inactive, during a new hair cycle – when new hair growth occurs – they activate quickly. However, they sometimes fail to activate, which is what causes hair loss.

In their article, “Lactate dehydrogenase activity drives hair follicle stem cell activation,” Christofk and Lowry found the metabolism of hair follicle stem cells is different from other cells of the skin. They soak up a form of sugar from the bloodstream called glucose and then process it to produce a metabolite called pyruvate.

This is the point they wanted to understand better. Under normal circumstances, the cells either send pyruvate to their mitochondria to create energy or they convert pyruvate into another metabolite called lactate. It was that point that the researchers thought might be a turning point for hair growth.

Was it possible that this was a fork in the road? If the cells send pyruvate to the mitochondria, does that mean the stem cells do not get activated? If scientists could somehow ensure the pyruvate instead is converted to lactate, could they increase the likelihood that hair follicle stem cells are activated?

“No one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells,” said Christofk in an article from UCLA promoting their discovery. “(These observations) 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,”

They started with mice, blocking the production of lactate genetically. They found that this step prevented hair follicle stem cell activation, which confirmed how essential the presence of lactate is for hair growth.

That was one piece of the puzzle. The next was to determine what if any impact increasing lactate production could have. They collaborated with scientists at the Rutter lab at University of Utah, increasing lactate production genetically in the mice. The impact was significant. It successfully sped up the activation of hair follicle stem cells, which in turn sparked the cycle of new hair growth.

Christofk says their attention then turned to topical treatments that could be applied to a patient’s skin that could have the same or similar effect of increasing lactate production. They identified two drugs: RCGD423 and UK5099. When applied to the skin of mice, each compound promoted lactate production but in very different ways.

RCGD423: Originally invented to enable cartilage rejuvenation, it has generated a lot of excitement among researchers exploring ways to counter the effects of arthritis. Another set of researchers recently reported that they observed RCGD423 prevent cartilage degeneration in mice – something no current treatment has been able to do. What the UCLA researchers found is that RCGD423 effectively transmits information from outside the cell to the nucleus of the cell by activating a cellular signaling pathway called JAK-Stat. This activation increases production of lactate, which drives hair follicle stem cell activation and speeds up hair growth.

UK5099: Developed by Pfizer, this compound is currently sold for research purposes and is being used in all sorts of experiments, including research into treatments related to prostate cancer. It does exactly what the UCLA researchers wanted – inhibit pyruvate from entering the mitochondria, which forces the production of lactate in the hair follicle stem cells and accelerates hair growth in mice.

“We’ve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general,” said Aimee Flores, a predoctoral trainee in Lowry’s lab and first author of the study.

The researchers say this could be especially useful in treating people with hair loss associated with such factors as hormonal imbalance, stress, aging or chemotherapy treatment. That said, UCLA also is quick to point out that RCGD423 and UK5099 are both experimental and have not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

We at Arocha Hair Restoration always caution that while these advances that are coming virtually every month are very exciting, but they are many years, and perhaps even decades away from becoming medical treatments. Nonetheless, we will continue to keep you updated as researchers continue to learn about hair loss and hair growth.