I wanted to mention this good article in the New York Times on the amyloid hypothesis and Alzheimer's. That's a topic I've covered often here, but this is a good overview of the field. And it's a good overview of the field's big questions, too: is amyloid really the cause of Alzheimer's? Do we have any therapies that can slow amyloid deposition, or not? If so, do any of them actually show any real-world benefit to patients?
This gets into the broader question of biomarkers as well. The FDA is insisting, as they should, that any potential Alzheimer's therapy should show improvements in memory or cognition, not just improvements in number of plaques or the like. Getting that sort of data is very difficult, but it's really the only way to avoid yet another "You'd Have Thought That. . ." moment. We've been having too many of those over the last few years. As the FDA's director of neurology puts it:
“You only care if down the road the patient gets better,” Dr. Katz said. “What we are concerned about is approving a drug based on a lab test and being wrong about what happens to the patient clinically.”
With Alzheimer’s, Dr. Katz said, “the great fear is that maybe amyloid has nothing to do with the disease.” If that were the case, and the agency approved a drug that blocked amyloid formation, millions of healthy people could end up taking something useless or even dangerous. And because it takes so long for Alzheimer’s to develop, it could be decades, if ever, before anyone knew the drug did not work.
“It is a conundrum,” Dr. Katz said. “We all hope to get to the point in our understanding of the disease process where everyone in the field says: ‘Look. We know it now. Amyloid causes Alzheimer’s, and we have drugs that decrease amyloid.’ But we are not there yet.”
Biomarkers, ideally, are supposed to speed up drug development. But validating a good one might just as slow a process as if you didn't have a biomarker at all. What I worry about is a situation where the first people to discover these things end up with no chance to benefit from their work, but actually end up helping out other groups much more. And while there's a place for altruism in medical research, I doubt if making it the driving force will lead to success. . .