This Breakthrough Drug Wakes Up Sleepy Hair Follicles. It May Be the Ultimate Baldness Cure, Scientists Say.

4 min read

• Researchers have developed a new drug that regrows hair by reactivating dormant hair follicle cells.
• The approach is different than current treatments, which only slow down hair loss. It reactivates hair follicles by boosting the body’s natural availability of lactate, which directly affects the follicles’ ability to grow hair.
• Safety trials are done and a trial to test its effectiveness is planned for next year.

For millennia, thick, healthy hair has symbolized both masculine virility and feminine appeal. So when hair thins or disappears altogether—which happens to approximately 80 percent of men and 50 percent of women—the hit to self-esteem can feel almost existential. Soon, however, hair loss sufferers might have a new option in their toolkit. And if early results hold up, this drug could prove to be the most effective solution yet.

That’s because unlike existing treatments like minoxidil and finasteride, which merely slow down hair loss, PP405 sparks new hair growth. “PP405 wakes up dormant hair follicles, so the mechanism is very different,” says Heather Christofk, Ph.D., a biochemist at UCLA, whose lab helped develop the molecule. Their work is published in the journal Nature Cell Biology.

Typically, hair toggles through phases of activity and rest, governed by the hair-follicle stem cells. In periods of activity, these cells awaken and regenerate the hair follicle, developing into the different components that make up hair. But when they’re resting, the hair stops growing and eventually falls out. With illness, stress, or an unlucky roll of the genetic dice, these stem cells can become permanently dormant.

But Christofk and her collaborator, William Lowry, Ph.D., a stem cell biologist at UCLA, discovered a way to wake them back up.

“We found that hair follicle stem cells have a really different metabolism when they’re asleep versus when they’re active and giving rise to new hair,” Christofk says. Specifically, hair follicle stem cells that are “on” have more lactate, a key molecule for creating energy without oxygen. (Most cells create energy via a route that requires oxygen). So Christofk wondered whether increasing lactate levels in sleeping hair-follicle stem cells might switch them on.

To test their theory, the researchers took advantage of a quirk of mouse biology. Mice are born without fur and their first few rounds of hair growth are synchronized. In this initial period, then, scientists can pinpoint the timing of the stem cells’ active and resting phases with exquisite precision. In one experiment, for example, they bred mice in which they could turn off the gene for lactate dehydrogenase, the enzyme that produces lactate. Unlike their normal peers, who regrew their fur 70 days after being shaved, these mice remained bald. Analysis confirmed that the animals had low lactate levels in their hair-follicle stem cells, and that lactate has a positive effect on hair growth.

On the flip side, when researchers genetically impaired the mice’s ability to move pyruvate (a molecule that turns into lactate) into their mitochondria (the powerhouse of the cell), more of it was converted into lactate instead. As a result, these mice grew hair more quickly than their normal counterparts. The scientists then confirmed this by treating normal mice with UK-5099, a molecule that blocks the same pyruvate-moving protein. Those mice also sprouted hair earlier.

“It was remarkable,” Christofk says. “We saw hair growing on these mice at a time when they shouldn’t be growing hair.”

Lowry and Christofk soon recruited fellow UCLA professor and medicinal chemist, Michael Jung, Ph.D., who helped them design an analog of UK-5099—dubbed PP405, after a major thoroughfare in Southern California. Not only was PP405 better at inhibiting the protein that moved pyruvate into mitochondria, its action was confined to the scalp. “Even when we put it in the blood, it’s not stable in the blood,” Christofk says. This means it’s unlikely to cause side effects, a problem that plagues other drugs that treat hair loss.

The three collaborators founded Pelage Pharmaceuticals in Los Angeles to continue research on PP405, with the aim of bringing it to market. To date, the drug, applied topically to the scalp, has gone through two clinical trials to test safety. The next target: a trial to test its effectiveness, set to begin next year.

Still, as a scientist focused on fundamental mechanisms, Christofk is interested in how metabolism influences a cell’s decisions. We know that recreating the environment of an active hair-follicle stem cell (for high lactate levels) can awaken a dormant one, even when other signals are telling it to stay quiet. But how is lactate doing this?

Unfortunately, the answer to this question—which could spur other advances in regenerative medicine—may be a long way off. Federal funding for the project fell victim to the Trump Administration’s widespread cuts at UCLA. Christofk and her collaborators are now scrambling to find alternative sources of support.

Meanwhile, Pelage Pharmaceuticals will proceed with the next phase of clinical trials for PP405. And while Christofk wouldn’t speculate on a go-to-market date, she’s optimistic about the drug’s prospects. “We hope that it’ll be useful for more people, and also for people suffering from different types of hair loss” like chemotherapy-induced hair loss, she says.