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ST. LOUIS, MO – A recent study has revealed that an experimental anti-amyloid drug, gantenerumab, appears to significantly reduce the risk of Alzheimer’s-related dementia in individuals with rare, inherited genetic mutations that predispose them to the disease at a young age. The research, conducted by the Knight Family Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU) at Washington University School of Medicine, suggests that early intervention to remove amyloid plaques from the brain may effectively delay the onset of Alzheimer’s symptoms.
The study, published in The Lancet Neurology, involved 73 participants with genetic mutations that guarantee the development of Alzheimer’s in middle age. A subgroup of 22 participants, who began the trial with no cognitive impairment and received the drug for an average of eight years, saw their risk of developing symptoms drop from nearly 100% to approximately 50%.
“Everyone in this study was destined to develop Alzheimer’s disease and some of them haven’t yet,” said Dr. Randall J. Bateman, the study’s senior author. “We don’t yet know how long they will remain symptom-free—maybe a few years or maybe decades. In order to give them the best opportunity to stay cognitively normal, we have continued treatment with another anti-amyloid antibody in hopes they will never develop symptoms at all.”
The findings lend support to the amyloid hypothesis, which posits that the accumulation of amyloid plaques in the brain is a primary driver of Alzheimer’s disease. By removing these plaques, the drug appears to delay the onset of cognitive decline.
The study was an extension of the Knight Family DIAN-TU-001 trial, which began in 2012. Participants, who had no to very mild cognitive decline, were within 15 years before to 10 years after their expected age of Alzheimer’s onset. While initial results showed that gantenerumab lowered amyloid levels, cognitive benefits were not immediately apparent.
The extension trial aimed to investigate the effects of longer treatment and higher doses. However, it was terminated early in 2023 after the drug’s manufacturer, Roche/Genentech, discontinued its development.
Analysis of the data revealed that the longest-treated subgroup, who received gantenerumab for an average of eight years, experienced a 50% reduction in the risk of developing symptoms. This effect size is based on both the number of participants developing symptoms and the timing of symptom onset relative to their expected age.
The drug was associated with amyloid-related imaging abnormalities (ARIA), a known side effect of anti-amyloid drugs. ARIA rates were 30% in the extension trial, compared to 19% in the original trial, likely due to higher doses. Two participants experienced severe ARIA and were removed from the trial, but they subsequently recovered.
The Knight Family DIAN-TU has now launched the Knight Family DIAN-TU Amyloid Removal Trial, where participants are transitioning to lecanemab, another anti-amyloid drug.
While the study focused on individuals with genetic forms of Alzheimer’s, researchers believe the findings have implications for all forms of the disease. “If late-onset Alzheimer’s prevention trials have similar results to the DIAN-TU trials, there soon could be Alzheimer’s preventions available for the general population,” said Dr. Bateman.
The Knight Family DIAN-TU is also conducting the Primary Prevention Trial, which is evaluating the investigational drug remternetug in younger individuals with genetic predispositions to Alzheimer’s, aiming to prevent the disease from ever developing.
“These exciting preliminary findings hint very clearly at the potential role of lowering beta amyloid in prevention of Alzheimer’s disease,” said Maria C. Carrillo, Ph.D., Alzheimer’s Association chief science officer and medical affairs lead.
Disclaimer: This article is based on preliminary research findings. Further studies are needed to confirm these results and determine the long-term efficacy and safety of anti-amyloid drugs in preventing Alzheimer’s disease. The information provided should not be interpreted as medical advice. Consult with a healthcare professional for any health concerns.
