The Great Unbalding Draws Nearer

The Tressless sub-Reddit is the internet’s largest gathering place for the bald and balding. It has more than 400,000 members, many of them young men stunned that their follicles have betrayed them so early. They share photos of their thinning scalps, vent about their diminished sex lives and self-esteem, track infinitesimal fluctuations in the size of celebrities’ foreheads, and ask questions like “Is Propecia an acceptable name for a daughter?” Mainly, they talk treatment: what works and, more often, what doesn’t. “I think I am done for,” reads a representative post by a 21-year-old who tried the popular medications but kept shedding anyway. “Should I shave it all and accept defeat?”

The Tressless community’s biggest frustration may be with the lack of progress. Technology has advanced in almost every other domain — we have self-driving cars, ChatGPT, and earbuds that translate foreign languages in real time — but the best hair-loss treatments are decades old and only marginally more effective than a good toupee. “WTF have we been doing for the last 30 years?” one redditor asked recently, prompting a 336-comment complaint session that at times showcased a surprising level of scientific fluency, with users citing journal articles, biochemical pathways, a broad spectrum of documented side effects, and the convoluted mechanics of FDA approval to explain the shortcomings of the current offerings.

There are the standbys, minoxidil (often known by its brand name Rogaine) and finasteride (Propecia), which have been on the market since the ’80s and ’90s and are still the only drugs approved by the FDA for hair loss. They can help preserve the hair you have, but both come with downsides. To get the full benefits of topical minoxidil, you have to rub it into your scalp twice a day, every day, forever. There’s a pill version, too, but it can cause dizziness and heart palpitations. Finasteride works better for some, but only for men, and only if they’re comfortable with the risk of erectile dysfunction, which in some cases can be permanent. Dutasteride, finasteride’s off-label nuclear-strength cousin, is more potent but equally deleterious to boners. Meanwhile, hair transplants can occasionally work wonders, but they’re expensive and frequently require international travel. Then there are laser helmets, platelet-rich plasma injections, microneedling, and a galaxy of supplements, which tend to work better at enhancing primary treatments than on their own. No currently available treatment seems to work for everyone, and, crucially, none can reliably do the one thing everyone wants, which is regrow thick, mature hair on parts of the scalp that have already gone bald. Nothing ever has. Until — maybe — now.

Last year, Tressless members started posting about a new potential treatment for hair loss that landed on their radar after the American Academy of Dermatology’s annual meeting was rocked by some early trial data. The drug, called PP405, was developed by Pelage Pharmaceuticals, and it works differently than the usual medications. In pattern baldness, or androgenetic alopecia, hair follicles don’t disappear. They gradually shrink and start producing thinner, shorter “vellus” hairs instead of thick, pigmented “terminal” hairs. Eventually, they go dormant and stop producing hair altogether. Minoxidil and finasteride try to rescue those struggling follicles before they reach that point, the former by increasing blood flow, the latter by blocking the conversion of testosterone. But PP405 is more ambitious, aiming to revive follicles that have already shut down by reprogramming the metabolism of their stem cells. In theory, it doesn’t just slow hair loss; it reactivates the parts of the scalp that have already surrendered — and seemingly without side effects.

Tressless has seen many so-called baldness cures come and go, so the initial response to PP405 was cautious. It’s “very interesting” and could represent “a new mechanism of treating hair loss, if it bears out in further clinical studies,” noted the first post to mention it in March 2024.

But the mood didn’t stay cautious for long. As Tressless members dug into the science and began circulating screenshots from Pelage’s website showing how quickly PP405 could work, the tone shifted to barely contained euphoria. By the time Pelage officially announced the impressive results of its Phase 2a trial this past June, the sub-Reddit had already declared PP405 the drug that would finally change everything. “Sprinkle that PP405 on my scalp like I sprinkle salt on my steak,” one member wrote. “BLESS PELAGE AND BLESS PP405 GIVE ME THAT SHIT RIGHT NOW,” posted another. Someone even wrote a poem:

r/Tressless, raise your balding heads,

For soon, we won’t need those meds.

For perfect hairlines we strive,

The dead follicles we’ll revive.

The reason I still cling to life?

Pee-pee-four-zero-five.

On some days, it seems like PP405 is the only thing Tressless wants to talk about. Threads dissecting its mechanism and trial design routinely draw hundreds of comments. In theory, the drug won’t go to market for a few more years, and that’s assuming it clears regulatory approval, which is far from guaranteed. But that hasn’t stopped it from becoming the sub-Reddit’s obsession, a vessel for all of its members’ longing and desperation. As Ozempic and Viagra have made such age-old problems as obesity and impotence pharmacologically optional, could PP405 do the same for baldness? 400,000 redditors are praying it can.

Of course, it’s not just them. Pattern baldness affects roughly 80 percent of men and nearly half of women over the course of their lives. After decades of snake oil and broken promises, we may be approaching a real inflection point — not just in the science of hair loss but in how the world thinks about baldness itself. For centuries, losing your hair was considered one of life’s cruelest fates and the only dignified thing to do about it was often nothing at all, since the available fixes — wigs, plugs, spray-on dye — were somehow even more humiliating. That logic is shifting. Imperfect though many of them still are, treatments are losing their stigma; people who haven’t even started shedding are using minoxidil and finasteride prophylactically, and celebrities from LeBron James to Bradley Cooper to John Cena have seen their hairlines come triumphantly marching back, drawing praise instead of ridicule. Into this cultural moment comes PP405, possibly the big one, arriving just as we’re finally ready to embrace it. We may not be at the end of baldness, exactly, but for the first time it feels within sight — the faint stubble of hope.

Most blockbuster drugs come out of large pharmaceutical companies, backed by years of research and armies of scientists. PP405 started with three UCLA professors, a few lucky encounters on campus, and some leftover flesh donated by cosmetic-surgery patients.

In 2013, Bill Lowry, a UCLA professor of molecular, cell, and developmental biology, was studying skin cancer in mice when he made an unrelated discovery: The mice’s active hair-follicle stem cells showed unusually high activity of a metabolic enzyme called lactate dehydrogenase, or LDH. The enzyme was well known in cancer research, but it had never been studied in the context of hair growth. He shared the finding with his colleague Heather Christofk, a biological-chemistry professor whose office was nearby. Curious to see if LDH was doing something important, they procured a strain of genetically engineered mice that carried a “floxed” LDHA gene, or one that could be switched off in specific cells with a drug. Breeding them produced offspring in which LDH could be disabled in hair-follicle stem cells. Then the researchers shut off the cells’ LDH and shaved the mice. Normally, their fur would have grown back in four weeks. It never did.

“In experimental settings,” says Lowry, “the best way to figure out how something works is to turn it off and then turn it back on.” So they flipped the switch in the other direction. Christofk hypothesized that one way to stimulate LDH would be to delete a gene that codes for something called the mitochondrial pyruvate carrier, or MPC. MPC transports pyruvate, an important fuel molecule, into the mitochondria, where it’s used for energy. Block that pathway, and pyruvate accumulates, and — by an elaborate chain of intracellular events that is beyond the scope of this article — LDH activity ramps up. To test the idea, Lowry and Christofk bred another set of mice in which they could shut off MPC in their hair-follicle stem cells. They shaved the animals. After just two weeks, one of Lowry’s students noticed something odd. “Hey Bill,” the student said, “these mice are turning blue.” In mice, when hair follicles start waking up, they activate pigment cells in the skin. The color change indicated that new hair was on the way.

The next question was whether it could work in non-modified lab mice. So they tried dosing some with UK-5099, a chemical compound known to inhibit MPC. “The mice had tons of fur,” Christofk says. “I was like, ‘Oh my gosh, it’s really working. It’s growing hair crazy well.’”

Lowry and Christofk still can’t say for sure whether LDH deficiency causes baldness. “But what we’ve shown is that if you stimulate LDH activity in hair-follicle stem cells, the follicles are able to overcome the triggers of hair loss, whatever those triggers are, and start growing hair again,” says Lowry. He offered this analogy: “Hair-follicle stem cells are like Batman, waiting to spring into action. They sit in their lair — the stem-cell niche — with special tools and capabilities but do not use them until they see the Bat-Signal in the sky. In a stressed, or aged, or hormonally imbalanced scalp, no one is putting out the signal, so Batman stays in his lair. An MPC blocker is like Alfred getting in Batman’s face and telling him to go save the kitten in the tree or whatever.”

The researchers weren’t ready to declare victory yet, though. Plenty of drugs work in mice but don’t in humans, foiled by differences in immune response, physiology, and, in the case of topical drugs, skin thickness. Human epidermis is at least ten times thicker than mouse skin and therefore harder to breach. UK-5099 had no trouble slipping through a mouse, but in people it might just sit on the surface. So the team needed a new compound to block MPC with the power to infiltrate human scalps.

A little while later, Christofk attended a seminar on campus and happened to sit next to Michael Jung, a chemistry professor with a track record of translating lab science into real treatments; he had already created two FDA-approved drugs for prostate cancer. “I said, ‘Mike, you have to come work with Bill and me,’” remembers Christofk. “He came back to my office, looked at the structure of UK-5099 on my computer screen, and said, ‘Yeah, we can make a drug out of that.’”

Jung went to work designing dozens of molecular variations of UK-5099. To test the compounds, Lowry’s lab team applied them to freshly snipped human skin discarded by plastic-surgery clinics — a perk of being in L.A. “We started with belly skin from tummy tucks, which you can get by the yard,” says Lowry, though only at certain times of year. “Sometimes the supplier would tell us, ‘It’s going to be a while, because we’re entering summer and nobody wants scarring during bikini season.’” They soon found that skin removed during face-lifts worked better anyway. “The hair density was much higher in those, so that was a gold mine of hair-follicle stem cells,” Lowry says. Ex vivo skin survives for only three or four days once separated from its host, which wasn’t long enough to expect hair or even stubble. But as they applied Jung’s molecules, the team saw follicle stem cells activate and divide, some within 24 hours, a sign they were hitting their target. Eventually they landed on one molecule, and in 2018, Lowry, Christofk, and Jung founded Pelage Pharmaceuticals, named for the French word for a coat of fur. They called their drug PP405, in honor of the L.A. freeway that connects them all to campus.

But was it safe? Blocking MPC in the scalp might jump-start hair growth, but no one knew what would happen if PP405 entered the bloodstream and made its way to other tissues. In 2023, the first human-safety trial began. Sixteen male participants applied a topical gel version of the compound to their scalps nightly for a week. No PP405 showed up in their blood, and no side effects were reported. A larger Phase 2a trial followed in 2024, this time with 78 men and women, some using the gel daily for four weeks, others a placebo. (Because the mechanism by which PP405 works is gender agnostic, Pelage could safely test it on both men and women from the outset.) Again, the drug stayed local and the participants stayed healthy. It was reassuring, though not completely unexpected. “We chose this molecule on purpose because it’s not stable in the blood,” says Christofk. “By the time we tried it on live humans, we’d been feeding it to rats and pigs for months,” adds Lowry, “and none of them looked particularly sick.”

But then came a surprise. The Phase 2a trial was designed primarily to test safety, not effectiveness, and the participants used the drug for only about a month. Even so, some of them started growing hair. Among men with more advanced baldness, 31 percent of those treated with PP405 saw their hair density increase by 20 percent or more by the eight-week mark. Those numbers might not sound earth-shattering, but minoxidil and finasteride typically take six months, and usually longer, to produce any visible difference. “We were blown away,” says Qing Yu Christina Weng, Pelage’s chief medical officer. “After just four weeks, you wouldn’t expect any separation between the treatment group and the placebo group. And not only were they growing new hair where there wasn’t any before, it wasn’t peach fuzz or baby hair — it was proper, thick, terminal hair.” (Regulations prevent Pelage from sharing before-and-after photos.)

According to Weng, these initial trials have only begun to show what PP405 might be capable of. She suspects some of the participants who fell short of the 20 percent hair-density threshold during the eight-week window would have crossed it with more time. And while Pelage is currently focused on pattern baldness, Weng says the company’s drug may help with other forms of hair loss too, including those caused by chemotherapy, menopause, perimenopause, and GLP-1 drugs like Ozempic — “any hair-loss condition where the follicle is still preserved,” she says.

But PP405 is far from a done deal, and there’s still a long way to FDA approval. Early studies like this “are not designed to give the best sense of the overall efficacy of the medication,” says Arash Mostaghimi, vice-chair of clinical trials and innovation at Brigham and Women’s Hospital’s dermatology department, who helped design PP405’s Phase 2a trial. “So the results you’re seeing are more like, ‘Hey, by the way, we also saw this.’ I understand the enthusiasm, and I was excited by the data as well, but drawing any firm conclusions or comparisons based on this study would be reading into the results too deeply.” After all, scores of other drugs have seemed effective at this stage and fizzled later. “We don’t yet know whether the response to PP405 is durable, whether the hair that comes in is going to stay around,” says George Cotsarelis, a dermatologist and stem-cell biologist at the University of Pennsylvania. “They only looked at it for a short period of time. At this point, a lot of things will look great, but at six months, not so much, and then at 12 months even less.”

Investors, at least, are bullish. Pelage has raised more than $30 million so far, led by Google Ventures, the venture-capital arm of Alphabet. Phase 3 trials are set to begin in 2026. If the FDA continues to like what it sees, PP405, or whatever it would ultimately be called, could by some estimates reach the market a year or two after that.

But for those losing hair now, even a three-year wait might feel unbearable. None of the scientists behind PP405 are bald themselves — suspiciously, everyone at Pelage, in fact, has a beautiful head of hair — but they’ve come to appreciate how deeply the condition can affect people. The three main researchers have been inundated with emails from strangers begging to join upcoming trials. (Under clinical-trial protocols, they’re not allowed to know who’s enrolled, much less handpick participants.) “I’ve lost the desire to live after this,” one person wrote to Lowry in July. “There were no such cases in my family. In Russia, we have a lot of superstitions and everyone says that I’m cursed. And the doctors I was treated by were reluctant and wanted to get money. I took out loans to try different types of treatment. At least tell me what I can do.”

About seven or eight years ago, Bob started losing his hair. He noticed the bulk of the shedding after experimenting with steroids. (Bob is not his real name, and he insists on calling me from a blocked number, but he’s fine with me telling you that he is 26, lives in North Carolina, and has an engineering degree.) Since then, he’s worked his way through the usual gauntlet of treatments, starting with wellness-aisle remedies like rosemary oil — “I’m not usually a big pro-medicine guy” — and moving on to minoxidil and finasteride. The latter thickened his hair a bit but left him with a persistent “ball ache” and a reduced libido. So he started looking for alternatives on the bleeding edge of science.

“I’m on the Tressless sub-Reddit quite a bit, and for a long time I’ve been tracking different experimental compounds,” says Bob. “I’ve been following HMI-115 and GT20029” — early-stage drug candidates targeting the usual active-but-flagging follicles — “and I was watching pyrilutamide” — which once looked promising but failed to outperform a placebo in its 2023 Phase 3 trial. Naturally, he was keeping tabs on PP405, too.

Then, this past spring, Bob came across a post on Tressless about a compound called JXL-069. It had been mentioned in a 2021 academic paper by the inventors of PP405 as one of the UK-5099 analogs — later tested on face-lift skin — and the abstract had described it as showing “significant MPC inhibition activity.” That led some redditors to speculate that JXL-069 might actually be the same molecule as PP405 — or at least a close relative. While the structure of PP405 remains under wraps, JXL-069’s molecular recipe had been published, plain as day, in the Journal of Medicinal Chemistry. “There was a Tressless post that said, ‘Has anyone tried JXL-069? It might be PP405,’” Bob says. “So I started doing my own research and reading the patents, and it made sense.”

Intrigued, Bob contacted a friend he’d met on a peptides sub-Reddit who claimed to know how to source gray-market pharmaceuticals. Was it possible to synthesize a batch of JXL-069? His friend said it was. So Bob and 40 other Tressless members coordinated via Reddit DMs, pooled their money, and placed an order. His share — 200 milligrams, $275 worth, enough to last at least a year — arrived in powdered form in a jar in his mailbox. “I try not to ask my friend too many questions,” Bob says, “but I know it comes from a lab in China to a lab in the U.S. and then he gets it from there.” To make sure they weren’t just buying powdered drywall, the group sent a sample to an analytical testing lab, which seemed to confirm that the structure matched the published descriptions of JXL-069. (He sent me a photo of the lab report to verify.) That was good enough for Bob.

Even if it really is the active ingredient in PP405 — “We feel like this is definitely the right compound,” Bob says — he couldn’t just dump it on his scalp. Like any drug, it needs a delivery system, in this case a topical gel. PP405’s gel formulation is proprietary, so the Reddit experimenters had to improvise.“Some people in the group are using the gel that was used in the preclinical trials on mice, which we know from the studies,” Bob says. “Is that the same thing they used on humans? Maybe. Probably not. But at least we know it’s been tested before.” Others, including Bob, opted for a homemade mix using propylene glycol, a solvent found in topicals like minoxidil.

He started applying it before bedtime in mid-June and even bought a microscope to track his progress at the follicular level. “I sure as hell wouldn’t be putting this on my head if Pelage hadn’t already tested it in humans,” he says. “We placed our order before the Phase 2a results were announced, and I know that was still sketchy, but once they were, that gave me extra confidence.” He stores the powder in his fridge to keep it from going bad and mixes a month’s worth at a time.

Unsurprisingly, Pelage Pharmaceuticals says it does not endorse the limited-phase trial happening in Bob’s kitchen. “It’s hard to believe they even figured out how to make such an analog,” says Lowry. “But I can almost guarantee they are not treating themselves with PP405. Don’t believe everything you see on the internet, and certainly don’t put anything you see on the internet on your head.” The same goes for the alleged dupes of PP405 that are already being hawked across TikTok and a number of websites, including one that claims to be selling JXL-082, another of the molecules used in Pelage’s early experiments. “PP405 is currently in clinical trials as a new chemical entity,” Weng says. “The structure of the compound is patented and known only to Pelage and has not been disclosed. All platforms claiming to sell PP405 or equivalents are illegitimate, and we cannot verify what actual product is being sold.”

The structure of PP405 isn’t the only thing Pelage is keeping secret. Behind closed doors, the company is working on other as-yet-undisclosed projects with ambitions far beyond the scalp. PP405 is among the first clinically tested compounds built on the idea that reactivating dormant stem cells could unlock the body’s own regenerative powers, “and we see it as proof of concept,” says Pelage CEO Daniel Gil. “We’re actively investigating other potential applications of related compounds.” Like what? “I have to be a little careful, because there’s patent stuff I don’t want to step on,” he says. “But if you think about aging tissues in our body — can you get stem cells in those tissues to bring back some vigor?” In other words, it’s a good thing they started with hair because we’ll want it when we’re all living forever.

Then again, that may not come to pass. This summer, the Trump administration abruptly froze $584 million in federal grants to UCLA — citing alleged civil-rights violations tied to antisemitism and affirmative action — and is now seeking a $1 billion settlement to restore the money. “My current basic-research grant from the National Institutes of Health, which is a continuation of the work that led to this discovery on alopecia, was suspended last week,” Lowry tells me in early August. “I don’t know what interesting discoveries won’t be made the longer this thing stays suspended.” Even if that funding returns, there’s another threat looming. Congress is considering a bill, proposed by Republican representatives in New York and Florida, that would bar federally funded research from using animals, including lab mice.

An end to such research in the U.S. might just inspire more guinea pigs like Bob, who, as the guardrails of the scientific Establishment fall off, may be armed by the internet with just enough information and confidence to get themselves in trouble. By late July, he’d been taking JXL-069 — or whatever that is in his fridge — for five weeks, a week longer than any of Pelage’s official trial participants took PP405. I messaged him on Reddit to see how it was going. No side effects so far: “I’ve been feeling strong about the lack of risks,” he says. “It’s still early for any real new hairs to be coming in and thickened up to where they would be noticeable; however, I do feel like maybe some of my miniaturized hairs that were already there and growing are starting to thicken a little as well. Excited for the coming weeks to hopefully really know.”