More misery for the amyloid hypothesis

Further to our feature, a few weeks ago, on the state of health of the amyloid hypothesis – the dominant hypothesis to explain Alzheimer’s disease – comes news of yet another abandoned trial. This time the company is Merck and the drug under test is verubecestat, which inhibits the BACE pathway which produces the beta-amyloid protein. The trial, which has been running since 2012, was stopped because there were absolutely no signs of drug efficacy. Particularly worrying is the fact that this trial enrolled patients with mild to moderate symptoms of Alzheimer’s as opposed to previous trials which tended to target individuals with more advanced forms of the disease. Big pharma is testing the amyloid hypothesis to destruction by sticking to its core tenet that either inhibiting the production of beta-amyloid or hastening its removal from the brain is the correct route to curing Alzheimer’s and enrolling groups of individuals earlier and earlier into the disease process. In the meantime here are a couple of reflective articles published in the wake of the failed Merck trial. The first is a commentary by Derek Lowe in Science Translational Medicine and the second is an article in The Atlantic by Sarah Zhang.