Alzheimer's disease is in the news, as the first major preventative drug trial gets underway. I salute the people who have made this happen, because we're bound to learn a lot from the attempt, even while I fear the chances for success are not that good.
A preventative trial for Alzheimer's would, under normal circumstances, be a nightmarish undertaking. The disease is quite variable and comes on slowly, and it's proven very difficult to predict who might start to show symptoms as they age. You'd be looking at dosing a very large number of people (thousands, even tens of thousands?) for a very long time (years, maybe a decade or two?) in order to have a chance at statistical significance. And you would, in the course of things, be giving a lot of drug to a lot of people who (in the end) would have turned out not to need it. No, it's no surprise that no one's gone that route.
But there's a way out of that impasse: find a population with some sort of amyloid-pathway mutation. Now you know exactly who will come down with symptoms, and (unfortunately) you also know that they're going to come down with them earlier and more quickly as well. There are several of these around the world; the "Swedish" and "Dutch" mutations are probably the most famous. There's a Colombian mutation too, with a well-defined patient population that's been studied for years, and that's where this new study will take place.
About 300 people will be given an experimental antibody therapy to amyloid protein, crenezumab. This was developed by AC Immune in Switzerland and licensed to Genentech, and is one of many amyloid-targeted antibodies that have come along over the years. (The best-known is bapineuzumab, currently in Phase III). Genentech (Roche) will be putting up the majority of the money for the trial ($65 million, with $16 million from the NIH and $15 million in private foundation money). Just in passing, weren't some people trying to convince everyone a year ago that it only costs $43 million total to develop a new drug? Har, har.
100 people with the mutation will get the antibody every two weeks, and 100 more will get placebo. There are also 100 non-carriers mixed in, who will all get placebo, because some carriers have indicated that they don't want to know their status. Everyone will go through a continuing battery of cognitive and psychological tests, as well as brain imaging and a great deal of blood work, which (if we're lucky) could furnish tips towards clinical biomarkers for future trials.
So overall, I think that this trial is an excellent idea, and I very much hope that a lot of useful information comes out of it. But I've no firm hopes that it will pan out therapeutically. This will be a direct test of the amyloid hypothesis for Alzheimer's, and although there's a tremendous amount of evidence for that line of thought, there's a lot against it as well. Anyone who really thinks they know what will happen in this situation hasn't thought hard enough about it. But that's the best kind of experiment, isn't it?