A few months ago, experts were talking about the next generation of “disease-modifying” drugs that were expected to help treat Alzheimer’s disease by attacking amyloid plaque in the brain. In fact, they were arguing that any newly written treatment guidelines were likely to be quickly outdated by the advent of new, powerful drugs. Drug companies were also optimistic, developing all kinds of “anti-amyloid” drugs that were expected to fundamentally alter the course of the disease.
“Amyloid” is the stuff that gets in the brain in Alzheimer’s disease. The theory is that amyloid is toxic to the brain, setting up the slow burn we know as Alzheimer’s disease. Based on that theory, we’ve assumed that drugs that prevent amyloid from developing, or that promote its removal, are drugs that would be good for treating Alzheimer’s.
So the scientists of the world attacked amyloid with a vengeance, generating drugs to clamp down on the enzyme that produces it, on the process that causes it to crystallize in the brain, and developing synthetic antibodies designed to find and remove it like heat-seeking missiles. And they designed and launched clinical studies to prove once and for all that this would work.
And this past August, they reported that the drugs did indeed lower the amounts of amyloid in the brains of living patients. This is amazing all by itself when you consider that extracting amyloid from brain tissue at autopsy requires concentrated acid and worse. And it’s also amazing when you consider that the ability to monitor amyloid in living patients was a pipe dream 10 years ago.
But those facts were lost — because it turned out that although the drugs basically did as they were told, the patients were no better off as a result. There was less amyloid in the brain, but the brain did not work any better. So, what does this mean? And what do we do now?
Well, it means either that amyloid is not the problem after all, or it means that anti-amyloid strategies have to be started earlier in the game in order to be clinically useful. It also means that what Alzheimer’s researchers will do now — at OHSU and across the nation — is test the drugs in individuals who are at risk of Alzheimer’s but have either no or minimal symptoms. That is going to be the new focus in drug development for Alzheimer’s: early diagnosis, early intervention.