Clinical trial of Alzheimer's drug fails

Pharmaceutical company Eli Lilly regrettably announced this week that a clinical trial of its key Alzheimer’s drug, solanezumab, has failed to meet the primary endpoint.

Solanezumab targets beta amyloid — the protein that forms clumps in the brains of Alzheimer’s patients — to clear the rogue proteins out, in the hope that this will lessen the symptoms and slow the progress of the disease. But in a phase 3 study conducted in people with mild Alzheimer’s disease, patients treated with solanezumab did not experience a statistically significant slowing in cognitive decline compared to patients treated with a placebo.

Neuroscientists all around the world have their own theories as to exactly what went wrong with the trial — for instance, Professor Roxana O’Carare from the University of Southampton suggests that we “need to deal with the problem of removing amyloid, not just breaking it down”.

Professor O’Carare explained how fluid and waste are eliminated from the brain along very narrow pathways that are embedded within the walls of blood vessels, and that these pathways can fail in their function with increasing age and with the risk factors for Alzheimer’s disease.

“When a vaccine such as solanezumab is administered,” she said, “the sticky plaques of amyloid from the brain break down, but the excess waste and fluid (soluble amyloid) is unable to drain along the already compromised drainage pathways.”

Professor Peter Roberts, from the University of Bristol, is meanwhile unconvinced that there is “a clear relationship between amyloid deposition and deficits in cognition in humans”, saying its presence “might be a good indicator but does not prove causality”.

“There is still a polarisation of the scientific ‘camps’ with beta-amyloid versus tau hyperphosphorylation, right down to the chicken and egg arguments on which precedes the other,” Professor Roberts said, referring to the accumulation of another protein in the brains of Alzheimer’s patients. “Tau has received nothing like the attention that amyloid has by big pharma — they all jump on the bandwagon, unfortunately.”

Professor John Hardy, from University College London (UCL), expects future trials to shift their focus to BACE inhibitors, which block the enzyme Beta-secretase 1 (BACE1). These inhibitors are said to reduce amyloid formation, rather than targeting its removal.

If there’s one thing all the scientists agree on, it’s that the search for a cure for Alzheimer’s must continue.