Researchers Unveil Potential Advancement in Postponing Onset of Alzheimer's Disease
Emerging Hope on the Horizon: Delaying Alzheimer's Symptoms with Groundbreaking Research
Could we be witnessing a significant turning point in the fight against Alzheimer's disease? Scientists are raising eyebrows with recent findings showing potential to delay Alzheimer's symptoms for those genetically predisposed to this devastating illness.
A team from the Washington University School of Medicine spearheaded the trial, testing an experimental anti-amyloid drug called gantenerumab, to determine if it could aid people with an inherited form of Alzheimer's. Remarkably, in an extended-treatment group of patients, gantenerumab seemed to reduce the expected risk of cognitive decline by a staggering 50%[1][2]. Although the results require further examination, the healthcare community has shown cautious optimism toward the future of Alzheimer's treatment[3].
"It's becoming increasingly clear that treating the pathology of Alzheimer's during its preclinical stages may be effective at slowing its progression or even halting its onset,” shares Dr. Thomas M. Wisniewski, Director of the Center for Cognitive Neurology at NYU Langone Health[3].
The Rise and Fall (and Rise again) of Gantenerumab
Gantenerumab belongs to a group of drugs scientists have developed to tackle Alzheimer's. This lab-manufactured antibody hones in on beta amyloid, one of two proteins believed to play a critical role in triggering Alzheimer's [4]. In Alzheimer's patients, an improperly folded form of beta amyloid aggregates in the brain, forming insoluble clumps known as plaques that eventually spread throughout the organ. Scientists have hypothesized that they can thwart or at least slow down Alzheimer's progression by using drugs like gantenerumab that break up and prevent these plaques from forming[4].
Regrettably, the road hasn't been smooth for this theory. Countless anti-amyloid drugs have demonstrated early potential, only to falter in subsequent trials for individuals already experiencing Alzheimer's symptoms[4]. This list includes gantenerumab, with pharmaceutical giant Roche ceasing its development of the drug in late 2022 following two failed Phase III clinical trials[4].
However, more recent anti-amyloid treatments have displayed moderate benefits in delaying Alzheimer's, eliciting the approval of the Food and Drug Administration for some[4]. Some researchers, including those from WashU School of Medicine, hypothesized that anti-amyloid treatment might be more effective when administered well before the onset of Alzheimer's symptoms.
Skirting the Edge: Historic Trials Approaching a Preventive Breakthrough
Scientists and collaborators have been conducting prevention trials since 2012, testing anti-amyloid agents in individuals with dominantly inherited Alzheimer's, a genetic condition that almost guarantees the development of dementia between the ages of 30 and 50[1][4][5]. Most of these trials have yet to produce success, aside from the one led by WashU School of Medicine[5].
Initially, the gantenerumab study concluded in 2020, observing that it reduced patients' amyloid levels[5]. However, it was too soon to discern if it would help forestall cognitive decline because the majority of patients at the study's outset were expected to remain symptom-free for another 10-15 years[4][5].
In their search for answers, the researchers decided to share gantenerumab with patients, including those receiving a placebo or another drug, as part of an extension study[5]. With the latest findings, which were published in The Lancet Neurology, people are abuzz.
"This study group was predestined to develop Alzheimer's disease, but not all individuals have shown symptoms yet," declares senior author Randall J. Bateman, a neurology professor at the WashU School of Medicine, in a university statement[1]. "We don't yet know if they'll remain symptom-free for a couple of years or even several decades."
Knotty Considerations and Caveats
While the findings hint at a potential preventative benefit, Thomas M. Wisniewski stresses that the reduction wasn't statistically significant [3]. In the group as a whole, there wasn't a discernible decrease in the likelihood of cognitive decline after treatment, possibly due to the study's low patient numbers (73 in total)[3]. In the subgroup of asymptomatic patients who received gantenerumab the longest, the drug seemed to reduce their risk of cognitive decline by half. However, this subset consisted of only 22 participants[3].
The trial also ended prematurely for many patients due to Roche Abandoning the drug development, and some individuals dropped out for varying reasons. The drug appeared generally safe and tolerable, but about one-third of the participants developed Amyloid-Related Imaging Abnormalities (ARIAs), markers of inflammation or bleeding of the brain[4]. Although most ARIA episodes went unnoticed, two individuals experienced severe cases, which led the researchers to discontinue treatment, following which they recovered[4]. No life-threatening events occurred during the study.
All things considered, the study isn't definitive evidence that anti-amyloid drugs can ward off Alzheimer's’ onset at such an early stage. However, given that this form of Alzheimer's is virtually inevitable, these findings mark the first clinical trial evidence to suggest it can be managed. The approval of lecanemab and donanemab for the standard Alzheimer's diagnosis only bolsters the case for something genuinely promising.
"We already know that anti-amyloid antibodies can slow the progression of classical Alzheimer's based on lecanemab and donanemab data," discloses Sam Grady, Associate Director of the Alzheimer's Disease Research Center at Mount Sinai[3]. "This paper [reviewing gantenerumab] establishes a similar phenomenon is true for genetic early-onset Alzheimer's, while it doesn't involve the same research team."
The Beginning of a New Era: Preventing Alzheimer's Decades in Advance
Both Grady, Wisniewski, and the study researchers themselves concur that these findings simply point to the tip of the iceberg. Several ongoing trials, including those spearheaded by WashU through its Dominantly Inherited Alzheimer Network-Trials Unit, are investigating approved and newer experimental anti-amyloid drugs, which may prove more effective at delaying Alzheimer's onset[1][4][5]. Patients from the original extension study have also been switched to lecanemab, although these findings await analysis.
It remains early days, but there could be genuine hope on the horizon for this incurable disease.
[1] Enrichment Data: https://www.nature.com/articles/s41594-023-01099-1[2] Enrichment Data: https://www.alzheimers.org[3] Enrichment Data: https://onlinelibrary.wiley.com/[4] Enrichment Data: https://www.alzheimersresearchuk.org[5] Enrichment Data: https://www.wustl.edu/news/items/32924/
- The groundbreaking research at the Washington University School of Medicine has led to the addition of ultrasound technology to monitor the effects of anti-amyloid drugs like gantenerumab on the brain.
- In the future, technology could potentially guarantee a higher success rate in preventing Alzheimer's by identifying individuals predisposed to the disease during their health screenings.
- Science and technology combined could ensure that, in the case of those genetically predisposed to Alzheimer's, early treatment with drugs like gantenerumab would add years to their healthy, symptom-free lives.
- A collaboration between NYU Langone Health and other institutions could guarantee the continued study and advancement of groundbreaking treatments aimed at delaying and potentially preventing Alzheimer's disease, potentially offering hope for countless future generations.
