A new study from Washington University School of Medicine in St. Louis suggests that the experimental drug gantenerumab may help prevent Alzheimer’s-related dementia in people with genetic mutations that almost always lead to the disease.
The clinical trial involved 73 participants in their 30s, 40s, and 50s who had a family history of Alzheimer’s and carried genetic mutations known to cause an overproduction of amyloid in the brain.
Amyloid is a protein that accumulates and interferes with cognitive function, a well-known hallmark of Alzheimer’s disease. The participants were selected based on their proximity to the expected onset of symptoms, ranging from 15 years before to 10 years after the anticipated development of cognitive decline.
For the 22 participants who received gantenerumab for eight years, the risk of developing symptoms was cut from 100% to 50%. Researchers reported that these findings suggest the possibility of delaying the onset of Alzheimer’s symptoms and providing individuals with more years of healthy life.
Gantenerumab is a monoclonal antibody designed to target and eliminate amyloid plaques in the brain. The drug was developed by Roche in Switzerland and its U.S. affiliate, Genentech. However, its development was halted in 2023 after the companies’ own trials failed to meet their primary goal of slowing cognitive decline in people with early symptomatic Alzheimer’s disease.
Despite these setbacks, the study conducted by Washington University provided the first clinical evidence that early treatment aimed at clearing amyloid plaques before symptoms arise may effectively delay the onset of Alzheimer’s disease.
Senior author Dr. Randall J. Bateman, a professor of neurology at the university, noted that many participants in the study have remained cognitively normal even after more than eight years of treatment.
However, researchers acknowledged several limitations to the study. The rarity of Alzheimer’s disease caused by genetic mutations limited the number of participants, and the study initially started with lower doses of gantenerumab. Additionally, external controls were used, which could affect the reliability of the findings.
Safety concerns were also highlighted, as 30% of participants experienced amyloid-related imaging abnormalities (ARIA). These anomalies appear on brain scans as tiny spots of blood or localized brain swelling. While most cases resolved without treatment and did not cause symptoms, severe ARIA forced two participants to discontinue using the drug. Researchers stressed that there were no life-threatening adverse events or deaths during the study.
The potential for preventative treatment has raised optimism among experts.
Dr. Howard Fillit, co-founder and chief science officer at the Alzheimer’s Drug Discovery Foundation in New York, stated that the study demonstrates how early treatment targeting amyloid plaques can delay Alzheimer’s onset. He compared this approach to the treatment and prevention of other chronic diseases, expressing confidence that prevention may soon become a viable option for those at risk.
However, not everyone is ready to draw conclusions just yet.
Dr. Chris Vercammen, a physician specializing in geriatrics and palliative care, noted that more research is needed, particularly involving larger, randomized trials that include diverse populations and individuals with late-onset Alzheimer’s.
According to Vercammen, the current study focused only on high-risk individuals at the pre-clinical stage, leaving questions about the treatment’s effectiveness for those already experiencing cognitive decline.
Although the development of gantenerumab has been halted, researchers are continuing to evaluate other anti-amyloid drugs, such as remternetug, developed by Eli Lilly, to see if they may be effective in preventing Alzheimer’s disease.
Bateman expressed hope that future studies will yield positive results for the general population. He noted that some participants in the current study remain symptom-free even after reaching or surpassing their expected age of onset. His team is continuing treatment with other anti-amyloid antibodies in the hopes that these individuals will never develop symptoms.
Experts agree that while much work remains to be done, this study marks a significant step forward in the pursuit of treatments that could one day prevent Alzheimer’s disease from developing in those at risk.