A small trial of Merck’s verubecestat was primarily focused on assessing safety of the drug, but the findings suggest it effectively switched off the production of toxic amyloid proteins that cause sticky plaques in the brains of patients with Alzheimer’s disease. A leading theory of Alzheimer’s is that buildup of these proteins kill off healthy neurons, eventually leading to memory loss, cognitive decline and personality changes.
If verubecestat is also shown to slow the pace of mental decline – a crucial question that a major clinical trial currently underway should answer by this time next year – it could be the first new Alzheimer’s treatment to be introduced in over a decade.
“People are excited,” said John Hardy, a neuroscientist at the University College London who first proposed that amyloid proteins play a central role in Alzheimer’s disease. “This is a very nice drug and I’m sure Merck are feeling very pleased with themselves.”
In the trial, published last month in the journal Science Translational Medicine, 32 patients with early onset Alzheimer’s disease were treated with verubecestat daily for seven days. Healthy volunteers were also administered the drug for up to two weeks.
This was not long enough to identify changes in the buildup of plaques in the brain; however, samples taken from the cerebrospinal fluid surrounding the brain indicated that the drug had reduced levels of two compounds that are recognized as building blocks for toxic amyloid proteins.
Hardy said that these findings convince him verubecestat is effective at targeting the accumulation of plaques in the brain. The question remains as to whether this will convert into tangible cognitive benefits for patients.
“What we have to be worried about is that the plaques have set off other pathologies – that it is too late,” Hardy said.
Verubecestat is the first drug of its kind to reach Phase III in human trials. The current test involves a cohort of 2,000 patients with mild to moderate Alzheimer’s being treated with the drug for 18 months. The next one will involve 1,500 patients with early onset Alzheimer’s for two years.
The latter test is perhaps the most crucial in determining whether verubecestat could potentially lead to a cure, given that these types of medications are most effective when treating early symptoms of a disease.
Source: Nature World News