Author: peterjang73

Two of the most anticipated studies this year—large-scale, randomized, controlled, and double-blinded trials of the popular obesity and diabetes drug semaglutide for Alzheimer’s disease—have unfortunately ended in a dud.

Novo Nordisk, the makers of semaglutide, announced the disappointing trial results early Monday morning. The drug did not meaningfully slow down the disease’s progression compared to placebo, the trials showed. The company will now shut down the extension of these trials, though some experts and advocacy groups are still hopeful about the potential future of GLP-1 therapy for Alzheimer’s.

“While these results are not what we had hoped for, they will contribute to our understanding of this devastating and fatal disease,” said Joanne Pike, president and chief executive officer of the Alzheimer’s Association, in a statement sent to Gizmodo.

Early but unfulfilled promise

Semaglutide is the active ingredient in the diabetes drug Ozempic and the obesity medication Wegovy; it’s also currently available as an oral diabetes medication under the brand name Rybelsus. It mimics the naturally occurring GLP-1 hormone, which helps regulate our hunger and insulin production, among other things. Though not the first approved GLP-1 drug, semaglutide’s improved duration and potency have greatly changed the field of obesity medicine. The drug is significantly more effective at helping obese people lose weight than diet and exercise alone.

For years, various studies have suggested that GLP-1 medications like semaglutide may also be able to prevent or slow down the progression of dementia. On the basis of this promising research, Novo Nordisk commissioned the evoke and evoke+ phase 3 trials four years ago. These trials collectively involved 3,808 older adults (over age 55) with mild cognitive impairment or early Alzheimer’s disease. The participants were randomized to receive a weekly dose of oral semaglutide or a placebo.

As with past trials, semaglutide was generally safe and tolerable (common side effects tend to be gastrointestinal, such as nausea or vomiting). People on semaglutide did appear to have some noticeable improvements in biomarkers related to Alzheimer’s, according to Novo Nordisk. Ultimately, however, these improvements did not translate to real-world results. There was no significant difference in the progression of people’s dementia between the two groups, the company reported.

“Based on the significant unmet need in Alzheimer’s disease as well as a number of indicative data points, we felt we had a responsibility to explore semaglutide’s potential, despite a low likelihood of success. We are proud to have conducted two well-controlled phase 3 trials in Alzheimer’s disease that meet the highest standards of research and rigorous methodology,” said Martin Holst Lange, chief scientific officer and executive vice president of research and development at Novo Nordisk, in a statement.

The future of GLP-1s for dementia

Alzheimer’s disease is one of the most complex and devastating conditions we can develop. Even today, researchers still aren’t in agreement about the exact causes of Alzheimer’s, nor about the best approach to treating it. And this is far from the first time that a promising drug candidate for Alzheimer’s has failed to cross the finish line in late-stage clinical trials. So in many respects, these results aren’t too much of a surprise.

But there may yet be a silver lining to this flop. Given the biomarker findings, it’s still possible that a GLP-1 medication can slow the progression of Alzheimer’s, just not this particular one or in this particular way. There are newer GLP-1-based drugs, including many in development, that are generally more effective at treating obesity and diabetes than semaglutide. So perhaps that greater effectiveness can apply to Alzheimer’s as well. And there is precedent for this happening with other drug classes. After years of failure (and one controversial approval), there are now several anti-amyloid drugs available that can modestly slow Alzheimer’s progression.

Another consideration is timing. It’s possible that giving anti-Alzheimer’s medications to people at high risk of the disease—but years before they show any symptoms—can significantly slow its emergence, a hypothesis that trials of other drugs are currently testing.

Advocates like the Alzheimer’s Association are not fully abandoning their hopes that GLP-1 therapy for Alzheimer’s can help, at least not yet.

“Though this semaglutide pill did not help against Alzheimer’s, the field will continue to investigate this class of drugs, as they may act differently. And, the Alzheimer’s Association remains a fierce leader for this type of innovative research, and we believe it’s critical to continue investigating diverse approaches to treatment and prevention,” said Maria C. Carrillo, Alzheimer’s Association chief science officer and medical affairs lead, in a statement to Gizmodo.

Novo Nordisk’s announcement comes roughly a week before the company is expected to present the primary results of the two evoke trials at the Clinical Trials in Alzheimer’s Disease (CTAD) meeting in early December. These results may provide a better sense of where the drug came up short.

For now, though, these findings should also illustrate why clinical trial research is so important. Many lab or observational studies will tease the potential of an experimental or repurposed drug, only for later, more definitive trials to come up short. These preliminary studies are key to finding the drugs or interventions that can work, but we should always be mindful that they won’t pan out most of the time.

This is an especially relevant reminder with GLP-1 therapy, which has shown promise for treating conditions beyond obesity, such as alcohol addiction. Other studies have validated the benefits of GLP-1s for some health problems, such as heart disease. But this may not be the first and only flop we see with this drug class.

Hacker conferences—like all conventions—are notorious for giving attendees a parting gift of mystery illness. To combat “con crud,” New Zealand’s premier hacker conference, Kawaiicon, quietly launched a real-time, room-by-room carbon dioxide monitoring system for attendees.

Plants can be quite tough—they’ll survive forgetful caretakers, aggressive pets, and other potentially life-threatening events. Apparently, these threats don’t compare to what some plants are capable of surviving: the extreme conditions of outer space.

According to a new study published today in iScience, Physcomitrium patens—an extremely common moss species—can survive for 9 months outside of the International Space Station. What’s more, 80% of the moss spores came back to Earth intact and healthy enough to continue growing, breaking new ground in astrobiological research at the onset of humanity’s missions to the moon, Mars, and beyond.

“Space imposes multiple extreme stresses simultaneously, and we expected that nearly all the spores could die,” Tomomichi Fujita, study senior author and a biologist at Hokkaido University in Japan, told Gizmodo in an email. “Instead, many remained viable and apparently grew into perfectly normal plants. It also contributes to discussions about the resilience of life beyond Earth.”

Life beyond Earth

This is not the first time that researchers have tested how the extreme conditions of outer space affect Earth-born creatures. In fact, astrobiologists often recruit particularly sturdy creatures—typically microbes or other microorganisms like tardigrades—known to withstand harsh conditions on Earth. One experiment in 2005 sent lichen to space for around two weeks, whereas in 2022 researchers found cyanobacteria and fungi could withstand extraterrestrial conditions for months.

Moss, on the other hand, was already known for its remarkable survivability, being “among the earliest plants to colonize land,” and has been known to thrive in Antarctica, volcanic fields, mountain peaks, and more, Fujita explained.

“We wondered: If mosses could pioneer barren lands on early Earth, could their spores also withstand the environment of space and even contribute to future efforts to green the Moon or Mars?” Fujita mused. Physcomitrium patens was also genetically well-understood among researchers, making it the ideal species for analyzing the effects of outer space on the plant’s genetic material.

The moss, a dry, mature sporophyte—moss structures containing thousands of spores—launched to space aboard Cygnus NG-17 in early 2022 and returned to Earth in 2023, riding SpaceX’s CRS-16. Excluding brief storage periods, the moss lay exposed to space on a specially designed panel for 283 days (fun fact: that is three days less than the famous “stranded” Starliner crew from earlier this year, although these human astronauts were inside the ISS, not outside).

Moss life in space

While in space, the moss “endured vacuum, cosmic radiation, extreme temperature fluctuations, and microgravity,” Fujita explained. To put this into perspective, just the temperatures alone ranged from anywhere between -320.8 and 131 degrees Fahrenheit (-196 and 55 degrees Celsius). And so, Fujita’s team expected that “survival rates could be close to zero.”

“The biggest challenge was uncertainty,” he said. “We had no way of knowing how much damage the combined stresses of space would cause because such conditions cannot be replicated on the ground.”

To their—pleasant—surprise, they were totally wrong. Upon the moss’s return to Earth, Fujita’s team assessed the combined effects of such elements on the moss’s germination rates, growth patterns, photosynthetic activity, and cellular integrity.

They found that a shocking 80% of the spores survived the intergalactic journey, whereas nearly 90% of those remaining spores were able to germinate, or grow. The chlorophyll levels in the moss were generally consistent as well, according to the paper.

That said, the study focused on a single type of moss, meaning it may not capture the full extent of how mosses—or plants, for that matter—respond to similar conditions, the paper noted. Space experiments are generally difficult to conduct, but Fujita is determined to continue building on the latest findings.

“This is not just a story about ‘moss in space,’” Fujita said. “It is part of a larger scientific effort to understand how life adapts to extreme environments, how ecosystems might be built in closed systems […] It is also a powerful reminder that life is far more resilient than we often imagine.”