An experimental drug reduced the risk of developing symptoms of Alzheimer's disease by half in people with a rare genetic predisposition for developing the condition in middle age. The corresponding study was published in The Lancet Neurology.
Removing amyloid plaques with monoclonal antibody therapies is known to slow clinical progression in symptomatic Alzheimer's disease. Whether or not the drugs can delay onset in asymptomatic individuals, however, remains unknown.
A previous randomized, placebo-controlled phase 2/3 trial found that monoclonal antibody gantenerumab lowered amyloid levels in the brain and improved some measures of Alzheimer 's-related proteins. The trial recruited individuals between 15 years prior and 10 years after their estimated years to symptom onset who had either normal cognitive function or mild dementia.
From the trial, however, the researchers saw no evidence of cognitive benefit for asymptomatic individuals as neither the intervention nor the placebo groups among them experienced cognitive decline. The researchers thus launched an open-label extension trial to continue studying the cognitive effects of gantenerumab among participants with a high risk for Alzheimer's genetic mutation.
The extension trial included participants treated with gantenerumab, another drug, or a placebo during the original trial. Participants were treated for an average of 2.6 years in the extension trial.
Ultimately, the researchers found that removing amyloid plaques years before symptoms were expected to arise delayed symptom onset and dementia progression among those who were asymptomatic to begin with and treated the longest. Those in the longest-treatment group received gantenurmab for an average of eight years, and their risk of developing symptoms was reduced by 50%.
Meanwhile, for those who received gantenerumab only during the extension trial for two to three years after receiving another drug or placebo in the original trial, the researchers reported no observable effects on cognitive function. The findings suggest that prevention may only be achieved among participants who begin treatment years before onset.
"Partial or short-term amyloid removal did not show significant clinical effects. However, long-term full amyloid removal potentially delayed symptom onset and dementia progression. Our conclusions are limited due to the open-label extension design and use of external controls and need to be confirmed in long-term trials," wrote the researchers in their study.
Sources: Science Daily, The Lancet Neurology