<![CDATA[Estrogen shapes schizophrenia in women: onset peaks, dosing shifts, and relapse risk from periods to pregnancy, postpartum, and menopause.]]>
Scaling Stem-Cell Manufacturing for Therapies
Human pluripotent stem cells (hPSCs) have long been viewed as one of regenerative medicine’s most promising raw materials. Now, as more than 100 clinical trials evaluate hPSC-derived therapies for diseases ranging from Parkinson’s disease to heart failure and type 1 diabetes, attention is turning toward a crucial challenge: how to manufacture these cells reliably and economically at industrial scale.
According to Kevin Cyrys and Robert Zweigerdt, PhD, both of Hannover Medical School in Germany, the field has entered a new phase. Rather than simply demonstrating that stem cells can be grown in bioreactors, researchers are increasingly focused on creating robust production platforms that can deliver consistent quality across facilities and patient populations.
“Human pluripotent stem cells can serve as an unlimited, renewable ‘raw material’ for essentially any therapeutic cell product,” the authors wrote, highlighting the technology’s potential to overcome limitations associated with donor-derived tissues and organs.
The manufacturing challenge is substantial. While some therapies, such as treatments for age-related macular degeneration, require only tens of thousands of cells per dose, others may demand billions of cells for a single patient treatment. Conventional laboratory-scale methods are unlikely to meet such requirements efficiently.
To address this gap, developers are increasingly adopting three-dimensional suspension cultures in bioreactors. Compared with traditional two-dimensional cell culture systems, bioreactors provide tighter control over temperature, oxygen levels, pH, and carbon dioxide while supporting automated, closed-system manufacturing compatible with good manufacturing practice (GMP) standards.
The field has already demonstrated notable progress across multiple therapeutic areas. Researchers have developed scalable processes for producing cardiomyocytes, pancreatic islet cells, hepatocyte-like cells, neural tissues, and immune effectors derived from hPSCs. Some cardiac manufacturing platforms have reported production of billions of cardiomyocytes in liter-scale bioreactors, while immune-cell manufacturing programs have successfully expanded induced pluripotent stem cell-derived natural killer cells in 1–10 L systems while maintaining product quality.
Yet scaling production involves more than increasing cell yields. “Industrial-scale success depends on more than headline totals,” Cyrys and Zweigerdt note, citing the importance of volumetric productivity, production time, reproducibility, and integration of expansion, differentiation, and downstream processing into a coherent GMP-ready workflow.
Looking ahead, Cyrys and Zweigerdt argue that the next generation of stem-cell manufacturing will be defined by data-driven process control. They predict that AI-enabled systems will help move the industry from retrospective quality analysis toward real-time decision support, ultimately improving comparability between batches and strengthening product definitions across manufacturing networks.
Despite ongoing challenges involving cost, quality control, and regulatory compliance, the authors conclude that stem-cell bioprocessing has already crossed an important threshold. Scalable culture systems are no longer the primary obstacle. Instead, the focus has shifted toward engineering reliable industrial processes capable of transforming complex stem-cell biology into reproducible therapeutic products.
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Pakistan’s Massive Genetic Database Reveals Millions of Unique Variants
The Pakistan Genome Resource (PGR), one of the largest genomic studies ever conducted in South Asia, has revealed novel insights into gene function, disease susceptibility, and the translatability of preclinical findings to humans. Published in a Nature article, a collaboration between Novartis, Columbia University Irving Medical Center, and the Center for Non-Communicable Diseases, Karachi, Pakistan, examined 173,303 PGR participants, constituting 0.07% of the population of Pakistan, the fifth most populous country in the world.
The numbers alone are impressive, as the scientists identified more than 6.6 million coding genetic variants, with nearly half of them absent from existing global databases. But the PGR is particularly powerful not just because of its size but also because of the unique genetic structure of the population being studied with high levels of familial relatedness.
The study identified naturally occurring homozygous loss-of-function (LoF) variants in 6,476 genes, about one-third of all human protein-coding genes. The researchers confirmed several well-known genetic associations. For example, individuals carrying LoF variants in the APOC3 gene had significantly lower triglyceride levels, while variants in PCSK9 were linked to lower LDL cholesterol. While both genes are already important targets in cardiovascular medicine, the findings shore up the dataset’s credibility.
New links between genes and biological traits provide clues about conditions ranging from obesity and diabetes to liver disease and neurodegeneration. In one striking example, individuals lacking a functional version of the gene CIDEB, which has become a major target in metabolic research because rare mutations that inactivate the gene provide significant protection against liver diseases, appeared to have a lower risk of liver disease, strengthening the case for therapies that target this pathway.
Some findings provided new context to genes already being widely studied, such as LRRK2—a gene currently targeted by experimental Parkinson’s disease treatments. LoF mutations in LRRK2 showed signs of kidney dysfunction. It’s an observation that raises important safety questions and highlights why human genetic studies matter so much. Sometimes biology sends a warning before a drug reaches the market.
The research also challenged assumptions based on animal studies. A gene called PRDM9 is considered essential for fertility in mice. Yet several people in the PGR with completely inactive copies of the gene had healthy children.
Ultimately, the Pakistan Genome Resource is much more than a national database. It’s a reminder that human genetic diversity remains vastly underexplored. By studying populations that have historically been overlooked, researchers are uncovering entirely new biology that could lead to better treatments, safer drugs, and a more profound understanding of what makes us human.
The post Pakistan’s Massive Genetic Database Reveals Millions of Unique Variants appeared first on Inside Precision Medicine.
The “steroid olympics” were a circus—and a window into our culture
Testosterone. Methenolone. Nandrolone. Human growth hormone and EPO. Meldonium, modafinil, and mixed amphetamine salts. Clomiphene, anastrozole, levothyroxine, and liothyronine. Patches and capsules, creams and pills. A whole galaxy of steroids, metabolic modulators, and synthetic hormones coursing through the blood of a few dozen swimmers, sprinters, and weightlifters. And millions of dollars up for grabs for athletes who could break world records and usher in the age of superhumanity.
On Sunday, May 24, at a $50 million arena built in a casino parking lot in Las Vegas, I witnessed a libertarian thought experiment come to life. The inaugural Enhanced Games were the first sporting competition where participants were encouraged to take performance-enhancing drugs. The founders say they’re challenging dated sporting norms and helping to build a world where we can all live better, longer lives. Critics say the event is an embarrassment, that it glamorizes the use of dangerous substances and puts lives at risk.
The open-air venue was compact and decked out in bright blue, with a six-lane, 100-meter track down one side, a four-lane Olympic-length swimming pool down the other, and a weightlifting platform and stage at the front. You could see the golden façade of the Trump Hotel looming in the background. The scene had all the trappings of an NFL game, with the too-loud music and crowd work on the big screen—a “flex cam” gave the well-muscled an excuse to unveil their biceps. Between events, adverts flashed up for the line of performance products sold by Enhanced, the company behind the event: injectable peptides that supposedly support cellular energy and skin elasticity, daily supplement powders with names like “Stronger” and “Longer.”
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Australian swimmer James Magnussen was the first athlete to sign up with Enhanced but hasn’t broken any world records. He finished last in his two events in Las Vegas.
The day started with the weightlifters, under the blazing sun. But by 4 p.m., only one of them had even attempted a world-record lift. Two had pulled out injured. Some athletes were competing without taking drugs because of the money on offer, and as the competition went on, they had the better of their enhanced peers: Hunter Amstrong, a 25-year-old American swimmer and triple Olympic medalist, won the backstroke by more than a second. In the men’s 100-meter sprint, the non-enhanced US athlete Fred Kerley romped to an easy victory. “Man, they gotta do better than that,” he said of his doped opponents in his post-race interview. “They need to train a little harder, get on that shit a little bit more.”
At the bar, bodybuilders swapped before-and-after pictures and talked about their stacks, and VCs and finance bros traded LinkedIn details. Lukas Lakutsin, a 6-foot-10, 354-pound Russian bodybuilder who was milling around the entrance to the VIP suites, initially told me he didn’t use any performance-enhancing drugs. Except testosterone replacement therapy, of course. But he didn’t think that really counted. “I’m almost 34 years old,” he said. “I need to do this to stay strong.”
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Jeremy Sigal, an influencer and author, wore a USA tank top that showed off hugely muscled arms adorned with prison tattoos. He told me he was proudly natural, in both his health and his personal life. “I’ve got an exceptional credit score,” he said. He has written 12 books on marketing and leadership. Later, I looked up his most recent book online. It’s called Simp to Pimp: 10 Steps to Fix Why She’s Not Banging You and lists AI as a coauthor.
What I saw in Las Vegas probably wasn’t the future of sport. But it was a perfect encapsulation of our present moment, as Silicon Valley biohackers, alt-right looksmaxxers, Make America Healthy Again boosters, and longevity-obsessed scientists all vie to remake reality in their own image. For them, the Enhanced Games offered a glimpse of a future where medical advances push the human race to new heights, and where they never have to get old.
I’ve tracked Enhanced’s journey from a crazy idea scribbled on a napkin to a public company valued at $1.2 billion. Behind the scenes, there have been power struggles, life-changing victories, and moments of total farce. As I recently, finally, watched the games unfold, two questions bounced around my head: Were they right? And what does that mean for the rest of us?
In December 2022, the Australian entrepreneur Aron D’Souza flew to Miami to spend New Year’s Eve with his friend and mentor Peter Thiel. A decade earlier, D’Souza had helped Thiel orchestrate the lawsuit that bankrupted Gawker—a stunning revenge against the gossipy New York media blog that had outed him as gay. Now he was armed with a disruptive idea that he thought Thiel, the billionaire cofounder of PayPal and Palantir, would love. It was inspired by the buff bodies he’d been seeing at the gym, highlighting a disconnect between a workout culture where the use of steroids was an open secret and a sporting establishment where it was, at least on paper, an inviolable taboo.
His initial pitch was provocative and confrontational: a grand sporting event to rival the Olympic Games, where competitors could take any substance they wanted—their body, their choice. The first time I met D’Souza, in the spring of 2024, he had founded the company and attracted some initial investment but seemed obsessed with taking on the fat cats at the International Olympic Committee and reinventing sports (even though he didn’t seem to be a huge sports fan himself). On Enhanced’s Discord server, I found a folder full of memes with names like IOC Clowns.jpg. The whole thing felt very unserious.
That would change.
D’Souza told me that Thiel had previously introduced him to Christian Angermayer, a German biotech billionaire, who would come onboard at Enhanced. He’s funded clinical trials of psychedelics through his company Atai Life Sciences and is helping bring them into the medical mainstream as a treatment for depression and anxiety. Angermayer says he spotted an opportunity to do the same thing for steroids. What he really wants is to redefine medicine, he told me. Its focus has already changed from treating disease to trying to prevent it; actively enhancing people’s health, he says, is just the next logical step.
By early 2024, Angermayer had brought his own people into key roles. The team included Michael Sagner, an anti-aging expert and private doctor who works with many of Hollywood’s leading men, and Max Martin, who has the jawline and cheekbones of an Instagram looksmaxxing influencer and the boundless enthusiasm of a puppy. (He started his own enhancement program a few years ago, when he was just 27.) Sagner would head up Enhanced’s medical commission, making sure the games were safe for the athletes. It was Martin’s job to make sure they actually happened.
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Tensions sparked as D’Souza’s freewheeling style clashed with the more sensible image that Sagner and others were now keen to present. “It was not just his personality and his abrasive way of talking,” Sagner told me recently. “Even when he was briefed on a scientific fact, he would just completely ignore it and say something outrageous.”
But the more outrageous D’Souza got, the more attention his idea received. In February 2024, James Magnussen, a retired Australian swimmer, became the organization’s first official athlete, and Enhanced promised to pay a million dollars to him, or anyone else, who could break the world record in the 50-meter freestyle.
The notion of a “steroid olympics,” as many have dubbed the Enhanced Games, had been kicking around for decades—for instance, in a Wired article from the early 2000s and an SNL sketch from the 1980s. Two things helped finally make the Enhanced Games a reality. First, in November 2024, Donald Trump was again elected president of the United States. The Biden administration had been actively hostile to the games, but the founders saw a more receptive political environment in Trump world. Not long after the election, Enhanced announced a new tranche of funding led by 1789 Capital, a venture capital firm whose partners include Donald Trump Jr.
And second, in February 2025, an enhanced swimmer finished the 50-meter freestyle faster than anyone in human history. It wasn’t Magnussen, though. He had been injecting himself with testosterone to grow muscle, plus a cocktail of peptides that aimed to speed up recovery—but his journey hadn’t quite worked the way he’d planned.
A combination of reputational issues (no pools wanted to host his training) and physical complications (the regimen did help him get stronger, but he packed on so much muscle that it slowed him down in the water) meant he watched from the sidelines as the Bulgarian-Greek swimmer Kristian Gkolomeev—who had finished fifth at the Paris Olympics in 2024—came in two-hundredths of a second under the record and won a million-dollar payout from Enhanced. The idea has always been that breaking records would effectively prove the legitimacy of this enhancement project: Look what we can do now.
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Gkolomeev, though, had a different motivation for participating: “One successful year in the Enhanced Games and I could make as much as I would in almost 10 careers,” he told me not long after setting the new record (notably, wearing a kind of “supersuit” that’s been banned by World Aquatics since 2010). Enhanced was paying its athletes a regular salary, on top of any potential bonus. And he had a young family to support and feared that the four-year stretch to the next Olympics would be long and precarious.
In May 2025, with a world record in the bag and a friendly administration in the White House, Enhanced was ready to announce its first games: They’d take place in May 2026 at Resorts World in Las Vegas.
At the same time, D’Souza made another big reveal: Enhanced Performance Products, a line of supplements available for a monthly subscription. The Enhanced Games now seemed less like a sporting event and more like a loss leader for selling testosterone injections, GLP-1s, or a range of peptides that are claimed, with little scientific evidence, to improve sleep or skin elasticity. Perhaps it was all a brilliantly executed marketing stunt.
“The games themselves now seem almost secondary to what appears to be an online marketplace for hormones, peptides, and other performance-enhancing compounds,” says Astrid Kristine Bjørnebekk, a steroids expert at Oslo University Hospital. “From my perspective, this significantly changes the nature of the project. It is one thing to organize a closed sporting event built around controversial principles, but openly marketing and commercializing substances such as testosterone, hGH, GLP-1 drugs, peptides, and other pharmacological compounds is something else entirely.”
As the games approached, more athletes joined. Some were genuinely elite. The US sprinter Kerley—who is serving a two-year ban for missing three drug tests—had won silver in the 100 meters in the Tokyo Olympics and a bronze in Paris. Ben Proud, a British swimmer, had won silver at the Paris Olympics and dozens of medals at world and European championships and the Commonwealth Games. He had been mulling over joining the Enhanced Games ever since the idea first emerged, but the tipping point seemed to come when Gkolomeev’s record was announced.
Some participants, like Magnussen and another swimmer, Megan Romano, had been tempted out of retirement. Romano hadn’t swum competitively for almost a decade. Others were at the start of their careers but ready to cash in their chips and bid goodbye to Olympic dreams for a potential six-figure payday. The $1 million payouts were reserved for records in the two flagship events—the 50-meter freestyle and the 100-meter sprint—but winning any other event would mean a prize of $250,000, with an additional $250,000 bonus for setting a world record.
Athletes would get paid even if they just showed up and finished last—as much as $50,000. This is all on top of the salaries that stretched into six figures in some cases, making the payout from the games more than many athletes make in a year.
Sport’s governing bodies reacted to each new athlete announcement with fury. World Aquatics threatened to ban for life any athlete who participated in the games, even if they didn’t take any drugs. Enhanced responded with an $800 million antitrust lawsuit against the global swimming organization, the World Anti-Doping Agency, and USA Swimming, alleging misuse of monopoly power.
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In November 2025, a court in New York dismissed the case. Three days later, D’Souza, the mind behind the entire project, was out. A notice on Enhanced’s website said he had “transitioned out of the company’s day-to-day operations.” Martin would take over as CEO. “The investors basically said we need someone a bit more serious,” Sagner told me. In conversations, execs at Enhanced played down any suggestion of a feud—D’Souza was simply the ideas man, with little interest in the day-to-day dreariness of actually running a company. (Enhanced spokesperson Chris Jones wrote in a statement that “there is no tension between Aron and Enhanced that I’m aware of.” D’Souza did not respond to a request for comment.)
I got the sense that Enhanced, in its new iteration as a pharmaceutical subscription company, was almost embarrassed by the games. When I visited enhanced.com a couple of months before the event, they had been relegated to a sub-heading on the home page. D’Souza’s showmanship had helped get attention for what was becoming a run-of-the-mill telehealth business like Hims & Hers—albeit one well timed to take advantage of a shifting regulatory landscape around peptides, which Robert F. Kennedy Jr., the US secretary of health and human services, has been pushing the FDA to approve despite a lack of evidence that they’re actually effective.
Sagner is still loosely involved with Enhanced, but he says the medical commission was not consulted before it launched its line of performance products. (Jones did not respond to a question regarding this claim.) Sagner is scathing about what he sees as the “hype” around peptides. “I can tell you already, peptides do nothing,” he says—with the exception of human growth hormone and GLP-1. “The peptides that people use, black-market peptides that they buy online—they do nothing. We have tested them; 80% of them contain nothing. It’s saline solution, salt water, and some of them are contaminated.”
At the end of January 2026, a group of around 40 swimmers, weightlifters, and sprinters arrived in Abu Dhabi to start their individualized enhancement “protocol,” as Enhanced calls it. Officially, they would be taking part in a clinical trial, pending approval by the Abu Dhabi government and overseen by Guido Pieles, a Qatar-based cardiologist who has taken over the reins of Enhanced’s medical commission from Sagner.
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They would be allowed to choose only from a menu of specific FDA-approved drugs. Pieles broke them down into five categories: testosterone variants and growth hormones, which can both boost muscle mass; metabolic modulators that can tweak how the body burns fat; stimulants like Adderall to improve focus; and EPO, which can increase the amount of oxygen the blood is able to carry. While Enhanced’s team might recommend particular things, the athletes would have the final say on what they wanted to take, if anything. (As Oslo University’s Bjørnebekk points out, FDA approval “does not mean the substances are inherently safe, particularly not when used for enhancement purposes.”)
There would be regular blood tests, heart scans, and brain scans and access to the best training facilities money could buy. Pieles and others say the clinical trial will help inform the line of supplements Enhanced is offering consumers, but there’s actually very little overlap between the drugs the athletes were taking and the substances the company is currently selling.
Not long after they arrived in the Middle East, the athletes were awakened by the sound of explosions at a military base near their hotel. The US and Israel had struck Iran, and the Iranian regime was responding by peppering the region with missiles. “It wasn’t a pleasant situation,” says Andrii Govorov, the world record holder in the 50-meter butterfly, who a year earlier had become one of the first swimmers to join Enhanced. Govorov had some experience in these matters—back in Ukraine, he’d had a business selling cars that helped fund his swimming career, but he’d lost it after the Russian invasion.
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Swimming, sprinting, and weightlifting were the focus of the first Enhanced Games but in many ways the sports were the sideshow.
The conflict exacerbated delays in getting approval for the clinical trial and sourcing the drugs, and as a result, what was supposed to be a 12-week enhancement protocol got cut down to eight weeks. The athletes didn’t actually start taking the drugs until toward the end of March. For those who had always been clean, that represented the irreversible crossing of a line. “The first injection was very emotional, very tricky to navigate,” says Proud. “For me, that was the day I went from the Ben Proud that I always knew to a new person.”
Proud was joined in the enhancement program by his girlfriend, Emily Barclay, who had swum at college level without ever appearing at a major international event; she was working as a swimming teacher at a school in England. After that first injection, they left Abu Dhabi and spent a few days in Dubai as they reckoned with what they had done. “I just couldn’t be around the team,” Proud says. “I wanted to be by myself and feel those feelings, because it is a big deal to make that step, and I felt it.”
Those feelings were soon forgotten, though, as the drugs kicked in. Proud says he had incredible energy, and a drive to train that he hadn’t experienced before. Shania Collins, an American sprinter, says she had “increased strength, increased recovery, and increased mental clarity at practice.” Sagner and several athletes admitted there were some side effects: acne and some swelling around the joints; unwanted hair growth for the women, unwanted hair loss for the men.
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One thing the athletes wouldn’t talk about, though, is what drugs they were actually taking. They all had the same reason: not wanting to encourage copycats who might take enhancements without a doctor on hand to tailor programs to their needs.
The one exception was Thor Björnsson (testosterone, deca-durabolin, anastrozole, halotestin), a hulking Icelandic deadlifter and former World’s Strongest Man who played The Mountain on Game of Thrones. Björnsson first heard about the games on Joe Rogan’s podcast and was immediately interested. The rules for strongman competitions are somewhat less stringent than those for Olympic sports, though, and he actually had to reduce the number of substances he was taking to meet Enhanced’s FDA requirements.
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There is some debate over how much doping some of the athletes were actually doing. In a conversation last year, Gkolomeev told me he’d only really been “microdosing,” and he confirmed that his 2026 enhancement program was largely the same. Sagner says the doses the athletes were taking were a fraction of the amounts some Olympic athletes had been caught using in the past. I heard that a few athletes had decided not to take steroids or growth hormones and were only using modafinil, a narcolepsy medication that’s thought to improve focus.
The day before the games, I asked Angermayer what it would mean if clean athletes like Kerley and Armstrong won their events—what impact it would have on Enhanced’s business model of using sports as a showcase for its line of performance products if the people using those products didn’t actually win anything. “I know what you mean, but mostly our business model is headlines to drive attention,” he said. “Any debate is good for us.”
In early May, Enhanced began trading on the New York Stock Exchange with an initial value of $1.2 billion.
That same week, it was finally go time. The athletes and coaches left Abu Dhabi and flew to Las Vegas, where they were put up in five-star luxury at the Conrad hotel inside Resorts World while they made their final preparations.
When I got there a few weeks later, toward the end of May, I found it jarring to see these hulking presences walking around the casino in their Enhanced sportswear, weaving their way through packs of half-drunk tourists, with slot machines flashing in the background and cigarette smoke hanging in the air. I had expected the games to be a bigger deal within the city itself, but they were just one of a thousand things happening in Vegas that weekend—drowned out by a series of BTS shows at the football stadium, by the Golden Knights in the NHL playoffs, by No Doubt’s residency at the Sphere.
If this was a sporting earthquake, it was one whose tremors were mainly being felt online, where bodybuilding influencers livestreamed to their followers on Kick and Twitch, and where thousands watched on YouTube and Rumble. (D’Souza once told me he’d had “every major sports broadcaster” vying for the rights; in the end, Enhanced struck an exclusive streaming deal with Roku in the US.)
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On the morning of the games, Enhanced held a medical symposium that was supposed to provide a taste of the company’s long-term objectives. The first speaker was Bryan Johnson, the longevity-obsessed entrepreneur famous for plowing his personal fortune into wild attempts to reverse his aging: receiving transfusions of his teenage son’s plasma, measuring his nighttime erections, taking more than 100 supplement pills a day. He spends $2 million per year on all this, but he looked pale and vampiric as he delivered the slightly off-brand message that, really, the most important thing was getting a good night’s sleep: “You don’t need to chase IV infusions; you don’t need to chase crystals. You don’t really need to do much of anything.”
At 2 p.m., I took two escalators from the conference room down to the arena, where spectators were filtering in. Though it had cost $50 million, it had been constructed in just three and a half weeks, and it showed; on the media tour the previous day, there were still loose screws on the floor of the bleachers.
There were a few thousand seats in an open grandstand down one side, and two rows of VIP suites on the other. No tickets were sold, so it was a strange mix of invited guests, investors, and influencers, some of whom had reportedly been flown in from Los Angeles on a chartered jet. The rapper Tyga was the biggest name to grace the “blue carpet,” although I did also spot Fabio James, a Michael Jackson look-alike who has had surgery to make the resemblance even stronger. Rumors swirled that Peter Thiel might show up; they proved unfounded.
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A few hours before the doors opened, journalists got a stern message from the organizers trying to bar us from interviewing guests. Still, I talked to a Cambridge professor who wanted to use Enhanced as a case study in innovation for his MBA students, a retired Brazilian swimmer with the Olympic rings tattooed on his forearm, and a biotech investor wearing an Enron hat. Proud’s family and friends were sheltered from the blazing sun in the shadow of the big screen.
D’Souza was nowhere to be seen. Nor was he really mentioned at all—not during the introductory press conference, where Martin was introduced as the “founder of the Enhanced Games,” nor during the event itself, where the athletes showered praise on Angermayer and Martin. But the tens of millions D’Souza had banked from the stock listing likely softened any blow. Plus, he’s already moved on to his next provocative venture: an AI-powered arbitration platform designed to scrutinize the work of journalists on behalf of the rich and powerful.
As the sun set behind the hills, casting the arena in soft gold light, there were still no world records. That and the wins for clean athletes seemed to put the whole Enhanced project in jeopardy—the knives were already being sharpened online. I asked the organizers whether this threatened the legitimacy of the project.
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“Our response is that enhancements help athletes improve and, in some cases, break records. And yes, some non-enhanced athletes also won—because talent and ability also matter,” Enhanced’s Jones emailed last week. “Breaking world records is incredibly hard as the margin is infinitesimal, as we witnessed. Ignoring that 13 athletes some of whom 10 years later broke personal bests is disingenuous and selective reporting.”
Megan Romano was one of them, swimming faster in the 50-meter freestyle at 35 than she had at 22. And Emily Barclay knocked two seconds off her fastest time in the 100-meter freestyle, coming in second in that event and winning the 50-meter freestyle; she went home with a check for $375,000. “No one’s ever heard of this girl,” said Enhanced swim coach Brett Hawke afterwards. “She’s retired; she’s a nobody. She comes out tonight and swims a time that would have got a bronze medal in Paris.” For all the talk of “superhumanity” and pushing the boundaries of performance, making a 35-year-old feel 22 again is probably the perfect marketing message for the products Enhanced wants to sell.
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Enhanced’s executives say people should take enhancements only with medical supervision, but price could be a barrier to heeding that advice. The battery of health tests the company was giving its athletes in the run-up to the games cost $25,000 per athlete per month. The drugs themselves start at $75 a month and go up toward $200. While Jones says the products “are in line with industry price points,” there were almost certainly people watching who saw the drug-altered physiques of athletes like Gkolomeev or Magnussen and decided to find cheaper, less safe alternatives on unlicensed websites.
“Many of these substances require medical supervision and prescriptions, and several are associated with potentially serious long-term health consequences,” says Bjørnebekk. “Presenting them in this lifestyle-oriented and commercial format risks normalizing use while downplaying the medical risks and uncertainties.”
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Before the night was over, Gkolomeev again had the chance to right the Enhanced ship. The final event of the night was the men’s 50-meter freestyle swim. His 2025 time had been surpassed by the Australian swimmer Cam McEvoy (without a supersuit) at the China Swimming Open a couple of months before, so he needed to lose another two-hundredths of a second to beat the new record of 20.88 seconds.
Gkolomeev was wearing the same supersuit he’d used the previous year, and he’d shaved off his mustache for a little extra streamlining. But he messed up his start—doing four kicks instead of five—and was trailing Proud at the halfway mark. His long arms levered him forward, though, and he reached the wall in 20.81. The spectators were on their feet as “WORLD RECORD” flashed red on the big screen. Martin vaulted over the glass partition from the VIP suites, beaming, to embrace Gkolomeev. They had their record.
Or did they? Online, people shared screenshots from the video feed, purporting to show that the clock had stopped before Gkolomeev’s hand touched the pressure sensor at the end of the pool. An Enhanced spokesperson gave a statement to the Guardian dismissing this as “completely unfounded internet drivel.” But hey—live by the sword, die by the sword. It’s quite possible Gkolomeev didn’t care. He had another million in the bank.
It remains to be seen if it’ll work out so well for the other athletes. Enhanced organizers recently announced a prize of $10 million for anyone who can break Usain Bolt’s 100-meter world record in 2027. They are adamant that the games will happen again next year. If they don’t, dozens of sporting careers will be over, and the athletes will join the long list of victims of VC-backed disruption.
My personal prediction is that Enhanced will pivot away from the risk and uncertainty of a flagship event—the company’s valuation plunged by almost $800 million when markets opened after what was perceived as an underwhelming set of results in Vegas. I expect you’ll see individual stunts and challenges, tightly controlled and filmed for virality and probably featuring your favorite YouTubers—think Björnsson bench-pressing Jake Paul.
D’Souza’s initial idea has served its purpose by capturing the world’s attention. But that won’t necessarily translate into success either. Though the company has had plenty of hype over the last 12 months, SEC filings published as part of its stock exchange listing reveal that it generated only $2,755 in revenue from its enhancements business in the first three months of 2026. Would what happened in Vegas be enough to juice sales?
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As the athletes gathered on the stage to receive their prizes, Martin took the microphone and addressed the crowd. “Enhanced is culture,” he said. “We are at the pulse of where the world is going.” On this, at least, he’s probably right. Testosterone replacement therapy is rapidly moving into the mainstream, and while the science may still not be there on peptides, they have certainly exploded in popularity in the two years since Enhanced launched. And there are undoubtedly more substances yet to be discovered that will promise to improve people’s lives, or at least hold their appearance in stasis. The enhanced age is upon us, whether we want it or not.
As the fireworks went off and the Killers closed out the event with “When You Were Young” (“Congratulations to … whoever deserves it,” said frontman Brandon Flowers), I wondered what that might mean for us mere mortals. Invoking Hunter S. Thompson’s Fear and Loathing in Las Vegas in a story about drugs and Las Vegas may be a cliché, but it struck me that fear played a big part in all of this. Fear of missing out. Fear of getting old. Fear of never making a dime on your life’s pursuit. Fear of waking up one morning and seeing your flabby, sunken face in the mirror while everyone around you shines and grins and thrives with white-toothed, alien smiles.
SAEED RAHBARAN
But the big problem with Enhanced’s vision of superhumanity is the question of who gets to join in. “People will be able to enhance themselves if they have enough money,” Sagner had told me the night before the games. The rest of us, I fear, will just have to function as normal human beings.
Amit Katwala is a journalist and author covering science, culture, and where they collide. His latest book is Tremors in the Blood: Murder, Obsession and the Birth of the Lie Detector. He is based in London.
Dual-target gene therapy in Parkinson’s disease: a multicenter phase 1 trial
Nature Medicine, Published online: 10 June 2026; doi:10.1038/s41591-026-04436-0
Phase 1 results reveal that BBM-P002, a dual-target gene therapy co-delivering TH and DDC, is safe and well tolerated in Parkinson’s disease, with 12-month motor improvements signaling therapeutic potential.
AI Model Predicts Alzheimer’s Progression from a Single MRI Scan
Researchers at the University of California, San Francisco (UCSF) have developed an artificial intelligence model capable of predicting cognitive impairment and Alzheimer’s disease progression using only a single baseline MRI scan and basic demographic information. The approach, published in Nature Aging, could help make early Alzheimer’s assessment faster, more accessible, and less dependent on costly specialized testing.
Alzheimer’s diagnosis remains complex and resource-intensive
Alzheimer’s disease accounts for approximately 60% to 70% of dementia cases worldwide. Although structural brain changes and cognitive decline are hallmarks of the disease, accurately forecasting who will develop progressive impairment remains difficult.
Current diagnostic workflows often rely on multiple complementary techniques, including PET imaging, cerebrospinal fluid or blood biomarkers, genetic testing, and comprehensive neuropsychological assessments. While effective, these approaches can be expensive, time-consuming, and inaccessible in many healthcare settings.
MRI scans are among the most widely available clinical imaging tools for neurological assessment, but MRI data alone has historically struggled to capture the complexity and heterogeneity of Alzheimer’s disease progression when used in conventional AI frameworks.
To address this challenge, the UCSF team designed a multitask deep learning framework that combines domain-specific imaging knowledge with advanced machine learning methods to predict cognitive outcomes directly from structural MRI scans.
AI framework predicts cognition without invasive testing
Unlike many earlier Alzheimer’s prediction models, the new system does not require longitudinal imaging data, baseline cognitive testing, PET scans, or molecular biomarker analysis.
The researchers instead focused on extracting clinically meaningful information from a single baseline MRI scan. The framework was trained to perform several related tasks simultaneously, including tissue segmentation, Alzheimer’s diagnosis prediction, and estimation of both present and future cognitive performance.
A key innovation of the study was the development of a specialized image model that segments brain tissue into gray matter, white matter, and cerebrospinal fluid before generating cognitive predictions. According to the authors, this task-specific segmentation step allowed the model to learn biologically relevant spatial brain features more effectively than standard transfer-learning approaches.
Senior study author Ashish Raj, PhD, professor of radiology and biomedical imaging at UCSF, said the goal was to create a system that could be realistically implemented in routine clinical environments.
“Unlike previous approaches, our model does not require baseline cognitive assessment, specialized image pipelines, expensive PET scans, genetic analysis, or fluid proteomics, making it a fast, accurate, and easily implementable tool for most clinical settings,” Raj said in a statement.
Large imaging datasets improved robustness and generalizability
To train and validate the framework, the researchers used imaging and clinical data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including MRI scans, demographic information, diagnoses, and cognitive assessments.
The team also incorporated MRI data from the Human Connectome Project Young Adult cohort, which contains scans from healthy younger adults with minimal age-related brain atrophy. According to the authors, exposing the model to healthy brain anatomy improved its ability to distinguish pathological neurodegeneration from normal aging.
An external validation cohort from the Dallas Lifespan Brain Study was additionally used to test the generalizability of the framework across independent datasets.
The researchers reported that the multitask framework outperformed existing AI methods, including standard transfer-learning approaches, in predicting clinically relevant outcomes. The model generated accurate predictions for Alzheimer’s diagnosis, tissue segmentation, current cognitive function, and future cognitive decline using only baseline MRI data.
The study also reported improvements in computational efficiency and processing speed compared with more complex MRI morphometry pipelines commonly used in neuroimaging research.
First author Daren Ma, MSc, a machine learning specialist in the Raj Lab at UCSF, said the framework could help clinicians identify at-risk patients earlier and streamline referrals for advanced neurological evaluation.
“We reported meaningful gains in speed and performance over other pipelines, which could prove valuable in developing a quick clinical prediction of cognitive impairment prior to referring the patient to a more advanced imaging lab and/or a full neuroradiology report,” Ma said.
Potential implications beyond Alzheimer’s disease
The researchers believe the framework could eventually be adapted for other neurodegenerative disorders characterized by structural brain changes and progressive cognitive decline.
Potential future applications include Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and Huntington’s disease. The ability to estimate cognitive impairment using minimal baseline data may also prove useful in community healthcare settings where access to specialist neuropsychological testing is limited.
In addition, the model may have implications for clinical trial design. Identifying likely disease progressors early could help reduce trial size requirements and improve patient selection for studies evaluating disease-modifying therapies.
“The ability to correctly predict progressors from non-progressors using only baseline data can dramatically reduce sample sizes and cost,” Raj said.
The authors emphasized, however, that further validation will be necessary before the model can be broadly implemented in routine clinical practice. Future iterations of the framework may incorporate additional clinical measurements where available, including longitudinal MRI imaging, PET scans, genetics, and blood or cerebrospinal fluid biomarkers.
The study highlights the growing role of AI-driven imaging analysis in neurology and suggests that clinically accessible tools such as MRI may eventually support earlier and more scalable prediction of Alzheimer’s disease progression.
The post AI Model Predicts Alzheimer’s Progression from a Single MRI Scan appeared first on Inside Precision Medicine.
Genetic and clinical investigation of insulin-degrading enzyme in Parkinson’s disease within the Chinese Han population
IntroductionGrowing evidence suggests a mechanistic link between type 2 diabetes mellitus and Parkinson’s disease (PD), with insulin-degrading enzyme (IDE) implicated in both insulin and amyloid-β metabolism, as well as α-synuclein degradation. However, the role of IDE in PD pathogenesis remains insufficiently defined. This study aimed to investigate the association of IDE gene polymorphisms and serum IDE levels with sporadic PD in a Chinese Han population.MethodsFourteen single nucleotide polymorphisms (SNPs) within the IDE gene were genotyped in 463 patients with sporadic PD and 576 age- and sex-matched healthy controls (HCs). An independent cohort of 100 PD patients and 100 HCs was used to quantify serum IDE concentrations. Correlations between IDE levels and clinical features were assessed. Logistic regression was employed to identify independent factors associated with PD.ResultsAmong the examined SNPs, rs11187007 showed a nominal allelic association with PD (P = 0.046), which did not survive the Bonferroni correction. Serum IDE concentrations were significantly higher in PD patients than in HCs (P = 0.015). Elevated IDE levels were negatively correlated with Mini-Mental State Examination scores (R = –0.230, P = 0.027) and positively associated with more severe symptoms. Logistic regression indicated that elevated serum IDE levels were associated with PD.ConclusionOur findings highlight that elevated serum IDE correlates with PD, suggesting a role for IDE in neurodegeneration, warranting further mechanistic and longitudinal studies to evaluate its potential as a therapeutic target in PD.
From autophagy–lysosomal deficits to neurodegeneration in Niemann-Pick type C1 disease: implications for age-related neurodegenerative disorders
Niemann-Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage disorder caused by loss-of-function mutations in the NPC1 gene. NPC1 deficit primarily disrupts lipid homeostasis and subsequently drives cellular degeneration through mechanisms involving impaired autophagy and mitophagy, mitochondrial dysfunction, and, recently demonstrated NAD depletion that links autophagy impairment to neuronal death. Emerging evidence also highlights the activation of innate immune signaling leading to neuroinflammation. In this review, we synthesize current mechanistic insights and describe how these molecular deficits are interconnected to drive neuronal death in NPC1 disease. We also discuss how these pathological processes parallel those observed in major age-related neurodegenerative pathologies such as Alzheimer’s and Parkinson’s disease. Finally, we highlight emerging therapeutic strategies that can potentially ameliorate these cellular deficits, offering avenues for mitigating neurodegeneration in NPC1 disease and other related neurodegenerative disorders.
RNA editing in Parkinson’s disease: emerging mechanisms, translational potential, and current challenges
Parkinson’s disease (PD) is a major neurodegenerative disorder characterized by progressive loss of dopaminergic neurons and accumulation of α-synuclein. Current treatments primarily focus on symptom alleviation, highlighting the necessity for identifying novel molecular therapeutic targets. RNA editing, as a post-transcriptional process that modifies RNA sequences without altering genomic DNA, is increasingly recognized as an important contributor to the neuronal development and synaptic regulation. Among known RNA editing types, ADAR-mediated adenine-to-inosine (A-to-I) editing is the predominant form in the brain. Accumulating evidence suggests that RNA editing patterns undergo significant alterations in PD patients. This review synthesizes current evidence within a three-layer framework: (1) evidence for RNA editing dysregulation in PD, emphasizing tissue-specific and context-dependent patterns; (2) downstream mechanistic pathways stratified by evidence strength; and (3) experimental models, translational applications, and limitations. A distinction between what is known versus what remains speculative is emphasized throughout. RNA editing changes in PD appear heterogeneous and context-dependent, with brain and peripheral blood showing distinct patterns. Whether editing changes represent disease drivers, compensatory responses, or downstream phenomena remains largely unresolved.
Brain Histamine Map Links Genetic Factors to Mental Health and Psychiatric Disorders
A study headed by researchers at King’s College London and the University of Porto has mapped the histamine system in the brain. Histamine, a molecule more commonly associated with allergies, plays a separate but poorly understood role in brain function. The new study addresses this gap, building the first multiscale map of the histamine system which spans from genetics to behavior and related mental health conditions.
The findings provide a new framework for understanding how this often-overlooked chemical system contributes to brain function and could point towards new treatment strategies for histamine-related conditions such as depression, ADHD, and schizophrenia. The study was funded by the National institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre.
Daniel Martins, MD, PhD, visiting senior research fellow at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London, said, “This work provides a crucial foundation for future research. By integrating molecular biology, brain imaging, and computational analysis, it offers a new perspective on how neurotransmitter systems are organized across the human brain. As neuroscience moves toward more integrated and personalized models of mental health, understanding systems like histamine may prove essential for unlocking new approaches to diagnosis and treatment.”
Martins is first and corresponding author of the team’s published paper in Nature Mental Health, which is titled “Mapping histamine pathway networks in the human brain across cognition and psychiatric disorders.” In their paper the team concluded, “This study provides an integrated characterization of the histaminergic system in the human brain, leveraging transcriptomic, neuroimaging, and functional datasets to delineate its molecular organization and relevance to brain function underlying cognition and psychiatric disorders.”
Histamine is a neurotransmitter, a molecule crucial for neurons to communicate with one another, the authors explained. “Neuronal histamine plays a crucial role in the regulation of brain function, serving as a neuromodulator with widespread influence across multiple neurotransmitter systems.” However, neuroscience research has classically focused on understanding other neurotransmitter systems such as dopamine and serotonin.
As the investigators noted, the organization of histamine in the human brain remains incompletely characterized. However, they explained, dysregulation of the histaminergic system has been implicated in a number of neuropsychiatric conditions, including anxiety, depression, schizophrenia, and autism spectrum disorder (ASD), as well as neurodegenerative diseases including Alzheimer’s, Parkinson’s, and Huntington’s diseases. “Therefore, targeting the brain histamine system has garnered significant attention as a potential new therapeutic strategy for treating these disorders, with pharmacological interventions aimed at modulating histamine receptor activity showing promise in preclinical models.”
Histamine acts through four known histamine receptors, which are responsible for how the signal will influence receiver neurons. Each of these histamine receptors, (histamine receptor H1 (encoded by HRH1), H2 (HRH2), H3 (HRH3) and H4 (HRH4)), mediates distinct functions. For their newly reported study, Martins and colleagues carried out what they described as multimodal analysis, integrating transcriptomic, neuroimaging, developmental and functional datasets to map the architecture of the histaminergic system.
To build a comprehensive map of how histamine acts in the brain, researchers first combined genetic and molecular data with physical maps of the brain.
This revealed which brain regions receive more input from the brain’s histamine system, and which parts show greater capacity to respond to histamine. These molecular data were then linked with positron emission tomography imaging of histamine receptors in living individuals, as well as functional neuroimaging databases that map brain regions to specific cognitive processes and mental health conditions. This type of scan shows how different parts of the brain are working by tracking a tiny amount of radioactive tracer in real time.
Their results found that different histamine receptors were found on brain cells that either turn activity up (excitation) or turn it down (inhibition). “The findings reveal that histaminergic genes exhibit distinct cellular and regional expression profiles, closely aligning with known histaminergic neuroanatomy and function,” they wrote. “At the single-cell level, histamine receptor H1 and histamine receptor H2 were enriched in excitatory neurons, whereas histamine receptor H3 showed preferential expression in inhibitory populations.” This suggests histamine may be important in maintaining the balance between excitation and inhibition, a fundamental property of healthy brain function.
Brain regions with higher histamine-related gene expression were consistently associated with processes such as emotional regulation, stress and fear responses, decision-making, impulsivity, reward, sleep, and memory.
The parts of the brain where histamine-related genes were most active also overlapped significantly with brain regions known to be affected in several psychiatric conditions, including attention-deficit/hyperactivity disorder, major depressive disorder, schizophrenia, and anorexia nervosa. This is in keeping with previous hypotheses linking histamine to these disorders. “By linking histaminergic gene expression to brain-cell types, neurotransmitter systems, cognitive domains and psychiatric disorders, these correlational findings generate several hypotheses concerning histamine’s critical role in brain organization, neurodevelopment and mental health, which further experimental mechanistic work should prioritize and build onto investigate causal relationships,” the investigators concluded.
Martins said, “Current psychiatric treatments largely target neurotransmitters such as serotonin and dopamine, yet histamine interacts closely with these systems and influences their activity. By providing a detailed map of histamine-related pathways, this work suggests new opportunities for developing treatments that target this system more directly, particularly for symptoms such as cognitive dysfunction, fatigue, and impaired motivation.
While these findings do not establish a direct causal role, they suggest that histamine signalling may contribute to regional vulnerability in these disorders. This aligns with a growing view in psychiatry that mental health conditions arise from disruptions across interacting brain systems rather than a single chemical imbalance.”
This new map paints a neural picture of a previously lesser-studied molecule. It opens up future avenues of research into exactly what histamine is doing in various cell types and parts of the brain.
“We want to emphasise that these findings are hypothesis-generating and based on large-scale datasets that capture patterns rather than direct mechanisms,” commented senior author Steve Williams, PhD, professor of neuroimaging at IoPPN King’s College London. Future studies will focus on testing how histamine signaling changes in living individuals, for example through pharmacological interventions or longitudinal imaging approaches.
Co-author Daniel Van Wamelen, PhD, clinical senior lecturer in neuroscience at IoPPN, King’s College London and one of the authors on the paper said: “This kind of work is already taking place at King’s College London, for example in the iMarkHD project. In this project we use Positron Emission Tomography scans to study a specific histamine receptor (called H3) in people with Huntington’s disease, an inherited condition that affects the brain. The goal is to see how histamine activity changes in different parts of the brain over time, and how these changes relate to symptoms such as apathy, depression, and anxiety.”
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