Hopes have been raised that millions of people could be spared the pain of Alzheimer’s disease, after a study found that a drug delayed the onset of symptoms in patients who were almost certain to develop it. Research in the US involved 73 people with rare, inherited genetic mutations which cause an overproduction of toxic amyloid protein in the brain. This meant they were all-but guaranteed to develop the condition by middle age, between their 30s and 50s.
Patients were treated with injections of the antibody drug, gantenerumab, every two weeks. In a subgroup of 22 people who took the drug for the longest — an average of eight years, the risk of developing symptoms was slashed from around 100% to 50%. Dr Randall Bateman, who led the research at Washington University School of Medicine, said: “Everyone in this study was destined to develop Alzheimer’s disease and some of them haven’t yet.
“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.
“What we do know is that it’s possible at least to delay the onset of the symptoms of Alzheimer’s disease and give people more years of healthy life.”
Brain changes linked to Alzheimer’s are thought to begin years, or even decades, before symptoms begin. The breakthrough comes from an extension to an earlier Alzheimer’s prevention trial led by the Knight Family Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU).
It found that gantenerumab lowered amyloid levels and improved measures of proteins related to the disease. But that research did not last long enough to prove the treatment could delay symptoms.
The study was then extended and all participants offered the drug. This meant there was no placebo group for comparison. Researchers instead used data from related research to estimate the age at which patients would normally have developed symptoms.
They then estimated that taking the drug for eight years roughly halved the risk of developing symptoms. Other patients who took the drug for only two or three years did not see the same benefits, suggesting early intervention was crucial.
Although the trial was limited to people with a genetic form of early onset Alzheimer’s, Dr Bateman said he hoped the findings could have implications for all forms of the disease.
He added: “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.
“I am highly optimistic now, as this could be the first clinical evidence of what will become preventions for people at risk for Alzheimer’s disease. One day soon, we may be delaying the onset of Alzheimer’s disease for millions.”
British researchers said the findings were promising but warned that the study, published in the journal Lancet Neurology, had some limitations.
Professor Charles Marshall, an expert in clinical neurology at Queen Mary University of London, said the suggestion that early treatment to reduce amyloid beta in the brain could delay symptoms was “very exciting”.
But he noted that the result came from “a secondary evaluation of a relatively small number of people who were treated for a long time, and therefore the results are not as certain as they would have been if they were the main trial result”.
Professor Robert Howard, an expert in old age psychiatry, UCL, challenged the researchers’ claim that the drug had lowered risk by 50%, describing it as a “misleading overstatement”.
Highlighting the lack of a control group, he added: “No responsible clinical trialist should claim on the basis of these data to have shown a 50% lowering of the risk of developing dementia symptoms.”
Professor Tara Spires-Jones, director of the Centre for Discovery Brain Sciences at the University of Edinburgh, said the study was “important scientifically as evidence that amyloid-lowering drugs may potentially be able to delay symptom onset”.
However, she also noted limitations including the lack of a control group, and the fact that the drug has been discontinued by manufacturer Roche “because it did not slow symptoms of the more common non-genetic forms of Alzheimer’s disease in a trial with over 1,900 participants”.
Prof Spire-Jones added: “While this study does not conclusively prove that Alzheimer’s disease onset can be delayed and uses a drug that will not likely be available, the results are scientifically promising.”
