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By Ed Cara Published March 19, 2025 | Comments (0) | Alzheimer's is currently incurable once symptoms begin, but scientists are hoping it's possible to stop its progression with early enough treatment. sfam_photo via Shutterstock We might be on the precipice of a pivotal moment in Alzheimers disease research. In clinical trial data released this week, scientists have presented early evidence that its possible to delay symptoms in people genetically fated to develop Alzheimers at a young age. Researchers at the Washington University School of Medicine led the study, which aimed to test whether an experimental anti-amyloid drug called gantenerumab could help people with an inherited form of Alzheimers. In a subset of patients treated the longest, the drug appeared to reduce their risk of developing symptoms as expected, by 50%. The findings will require a follow-up, but outside experts are cautiously optimistic about what this could mean for the future of treating Alzheimers. The results make it clear that there is good hope that treatment of [Alzheimers] pathology in the preclinical stages of pathology may be effective at slowing or preventing disease onset, Thomas M. Wisniewski, the director of the Center for Cognitive Neurology at NYU Langone Health, who is not affiliated with the research, told Gizmodo. Gantenerumab is one of many similar drugs that scientists have developed for Alzheimers. Its a lab-made antibody that targets beta amyloid, one of two proteins thought to play a critical role in causing Alzheimers (the other being tau). In people with Alzheimers, a misfolded version of amyloid beta builds up in the brain, forming into hardy clumps known as plaques that eventually riddle the organ. Scientists have theorized that its possible to stop or at least slow down Alzheimers with drugs such as gantenerumab that break up and prevent these plaques from forming.Unfortunately, it hasnt been a smooth ride for this hypothesis. Many anti-amyloid drugs have shown promise early on, only to fail in larger trials that tested them for people already beginning to experience Alzheimers symptoms. That list includes gantenerumab; in late 2022, pharmaceutical company Roche shut down its development of the drug after a pair of Phase III trials failed. But more recent anti-amyloid drugs have demonstrated a modest but noticeable effect in slowing down Alzheimers, enough to win approval from the Food and Drug Administration. Some researchers, including at WashU Medicine, hoped that anti-amyloid treatment could be more effective when administered long before the appearance of Alzheimers symptoms. Starting in 2012, the researchers and others launched prevention trials testing anti-amyloid agents in people with dominantly inherited Alzheimers, a genetic condition that all but guarantees the development of dementia sometime between a persons 30s and 50s. Most of these trials havent yielded success, except possibly for the one with gantenerumab. When the original gantenerumab study concluded in 2020, the researchers found that it reduced peoples amyloid levels. But it was too early to know whether it might delay peoples symptoms, since most patients at the start of the study werent expected to become sick for another 10 to 15 years. The researchers then decided to openly provide gantenerumab to its patients (including those who were taking a placebo or another drug) as part of an extension study.Everyone in this study was destined to develop Alzheimers disease and some of them havent yet. Its the latest results from this study, published Wednesday in The Lancet Neurology, that has people excited. Everyone in this study was destined to develop Alzheimers disease and some of them havent yet, said senior authorRandall J. Bateman, a professor of neurology at WashU Medicine, in a statement from the university. We dont yet know how long they will remain symptom-freemaybe a few years or maybe decades.That said, there are important caveats to the study. For one, the findings only hint at a potential preventative benefit, Wisniewski notes. Though the drug may have reduced the risk of cognitive decline in the overall larger group of symptomless people, this reduction wasnt statistically significant (possibly because of the studys low patient numbers, 73 in total, Wisniewski says). In the subset of asymptomatic patients who were treated the longestabout eight years on averagethe drug seemed to reduce their expected chances of cognitive decline by 50%. But this subset only included 22 patients, an even smaller sample size. The trial also ended earlier than expected for many patients due to Roches abandonment of the drug, and some people dropped out for other reasons. The drug appeared to be generally safe and tolerable, though about a third developed amyloid-related imaging abnormalities, or ARIAs, which are markers of swelling or bleeding of the brain. ARIAs are a known side-effect of these drugs, though most episodes are unnoticed by patients. Two patients did experience severe ARIAs, which prompted the researchers to stop treatment, after which they recovered. No life-threatening events or deaths were reported during the study.All in all, the study is not definitive proof that anti-amyloid drugs can work for Alzheimers this far in advance. But since this form is essentially inevitable, these results are the first from a clinical trial to suggest it could be treated. Coupled with the earlier approvals of lecanemab and donanemab for the classical version of the neurodegenerative disorder, there does seem to be something real here. We already know from the lecanemab and donanemab data that anti-amyloid antibodies (AAAs) can slow progression of common, sporadic Alzheimers, Sam Grady, associate director of the Alzheimers Disease Research Center at Mount Sinai, told Gizmodo. This paper focuses on using a different AAA (gantenerumab) to demonstrate a similar phenomenon is true in genetic early onset Alzheimers, added Grady, whos not affiliated with the new research. Grady, Wisniewski, and the study researchers themselves all agree that this is only the beginning. There are indeed prevention trials ongoing right now for both early-onset and classic Alzheimers, including several being run by WashU through its Dominantly Inherited Alzheimer Network-Trials Unit. These trials are testing approved and newer experimental anti-amyloid drugs that could show even more of a protective benefit than gantenerumab. The researchers were also able to switch many of their patients in the original extension study to lecanemab, though the data from this phase remains to be analyzed.Its early days, but there might be genuine hope for this incurable disease on the horizon.Daily NewsletterYou May Also Like By Ed Cara Published March 17, 2025 By Ed Cara Published March 16, 2025 By Matthew Gault Published March 10, 2025 By Ed Cara Published March 4, 2025 By Ed Cara Published March 2, 2025 By Ed Cara Published February 6, 2025
