Failure of developmental Alzheimer's drug has wider implications

Posted Feb 17, 2017 by Tim Sandle
News that pharmaceutical company Merck has halted a clinical trial for a once promising Alzheimer’s treatment (verubecestat) is not only bad news for the patient group, it could signal that the general view as to the cause of Alzheimer's might be wrong.
PET scans showing the differences between a normal older adult s brain and the brain of an older adu...
PET scans showing the differences between a normal older adult's brain and the brain of an older adult afflicted with Alzheimer's disease.
National Institutes of Health
Merck have abandoned their experimental study after concluding that there is no prospect of the drug actually working. This is an expensive, but not uncommon, occurrence in pharmaceutical drug development. What is of concern is that the drug aimed to directly deal with amyloid plaques, which are regarded by most medical opinion as the causative agent of Alzheimer's disease.
It is established that amyloid plaques form in patients with Alzheimer’s disease. These plaques are a form of adhesive build-up that can accumulate outside nerve cells. The plaques occur when a common protein divides improperly (and produces folding). It is thought that this protein becomes toxic to neurons in the brain (and that this causes neural death, leading to Alzheimer's disease.) Such theories are based on the build-up of plaques observed through autopsies of patients who have succumbed to Alzheimer's.
What the Merck’ medication did, when tested out on a volunteer group who had mild or moderate Alzheimer’s, was to switch off the production of amyloid in the brain. The drug did this successfully but it made no difference to the progression of the disease.
The reason for the despondency in medical circles is because the Merck issues comes only two months after the failure of another Alzheimer’s drug called solanezumab (as reported by New Scientist magazine). This drug also targeted beta amyloid plaque.
What the two drug failures signal is that although amyloid plaques are associated with Alzheimer's disease, plaque formation may not be the cause. While it is probably a little early for this to be a concrete assertion, it at least suggests that other forms of research into the disease are required. An alternative hypothesis is that once amyloid plaques begin to form it is too late to prevent the disease and any drug that aims to slowdown or to halt further formation is doomed to failure.
Speaking with New Scientist about the Merck announcement, Bryce Vissel at the University of Technology Sydney in Australia, who has been studying Alzheimer's disease for many years, stated: “It’s my strong view that new approaches need to be developed, and new directions in research supported.”