An Anonymous Coward writes:
Dr. Derek Lowe, from In the Pipeline, writes about another disappointing failure to treat Alzheimer's Disease:
Merck announced last night that the first Phase III trial of their beta-secretase (BACE) inhibitor verubecestat was stopped because of futility. The monitoring committee, after looking over the data so far (the trial's been running since 2012) concluded that there was no real chance of seeing efficacy.
[...] The list of Alzheimer's clinical failures is impressive, but the list of failures to clinically validate the amyloid hypothesis is even more so.
[...] Beta-secretase inhibitors have failed in the clinic. Gamma-secretase inhibitors have failed in the clinic. Anti-amyloid antibodies have failed in the clinic. Everything has failed in the clinic. You can make excuses and find reasons – wrong patients, wrong compound, wrong pharmacokinetics, wrong dose, but after a while, you wonder if perhaps there might not be something a bit off with our understanding of the disease. Remember, every time one of these therapies comes around, it builds on the failures before it. Better and better attempts are made – I mean, verubecestat seems to be a pretty good compound, from the preclinical drug discovery perspective. It's surely the best swing anyone's taken at beta-secretase (and there have been many). But it just flat out did not work.
The good news about this study is that it adds to the evidence that the amyloid hypothesis of Alzheimer's Disease is a blind alley and that the presence of amyloid plaques is simply correlative and not causative. As more data comes in from the study, I hope that the evidence will be conclusive enough that more effort will be spent on pursuing other therapeutic targets.
See also: https://en.wikipedia.org/wiki/Alzheimer's_disease#Amyloid_hypothesis
Prions also form amyloids and their formation directly induces disease. How is it obvious that the amyloids in Alzheimer's are benign?
Populations with genetic determinants that specifically predispose them to producing amyloid beta in the brain develop early onset Alzheimer's at a much higher rate than non-carriers. How is it obvious that all these cases are simply a coincidence?
Populations with genetic determinants that predispose them to have inefficient clearance of amyloid beta in the brain have increased Alzheimer's risk than non-carriers. How is it obvious that these cases are a coincidence?