For decades Alzheimer’s research was centered around one theory, the amyloid-beta hypothesis. That theory is now being called into question after evidence of potential fraud.
Radio Advisory’s Rachel Woods sat down with life sciences expert Nick Hula and senior care expert Miriam Sznycer-Taub to talk about what this means for the scientific and medical community, how to restore trust in medical research, and where the industry may look to next when it comes to memory care.
Rachel Woods: This last, I think it was July, news broke that some of the key research supporting the leading hypothesis for Alzheimer’s was actually pretty darn manipulated. Tell us what actually happened.
Nick Hula: To start, Alzheimer’s disease is one of the top 10 leading causes of death in the United States, and most people who have it are never even diagnosed with it. It’s probably a lot higher. But even though it is an incredibly deadly disease, one of leading causes of death in the United States, we don’t actually know what causes it.
Woods: Still?
Hula: Still to this day. And for decades, we have had a hypothesis that it is these proteins called amyloid plaque. And for decades, there’s a lot of research around what types of these plaques could potentially be causing Alzheimer’s disease, how is this leading to memory loss? But there was never any definitive study that tied this amyloid plaque to memory loss.
That is, until 2006 when a study was done at a lab at the University of Minnesota that showed in mice or rats, not in humans, but in mice or rats, that a specific type of this amyloid plaque directly was related to cognitive decline in those rats.
Woods: But it turns out that’s not the end of the story.
Hula: It turns out that’s not the end of the story. Because for the decade and a half that followed, there was this big group of researchers who really believed in this amyloid plaque hypothesis. They turned to this study as proof. However, this past year it came out that images from that 2006 study were essentially photoshopped.
Woods: Literally faked. They just took, was it the graphs, the results, they were just cutting and slicing photos together?
Hula: No one has access to the raw data, so we can’t know for sure. But there is overwhelming evidence that they were able to copy and paste pieces of the photo to make it look like their hypothesis was correct, when in reality, it most likely was falsified.
Woods: Which is literally the opposite purpose of science and scientific advancement. And it’s never a good thing when something like this turns out to be fraud. But why is it such a big deal for Alzheimer’s? Nick, I feel like you were going down this path already when you said, “We don’t actually even know the cause of this disease.” And this was a hopeful moment of trying to point us towards a cause. Why is that such a big deal for patients suffering from Alzheimer’s?
Miriam Sznycer-Taub: I think Nick alluded to the size of the Alzheimer’s patient population. It’s over six million that we know have a diagnosis. And as Nick mentioned, it’s a very underdiagnosed disease. There are probably millions more that are not diagnosed, but most likely have Alzheimer’s and the number’s growing.
And unfortunately, once given a diagnosis of Alzheimer’s, there’s not a lot that can be done. There’s no cure. There’s not even a ton of really effective treatments for the loss of memory and the loss of self. There’s certainly treatments for some of the side effects and some of the other medical conditions that come along with it. And people had been looking to this research as a sign that we were going to find something that would be helpful. And this is a blow in unfortunately a series of blows to finding an effective treatment for Alzheimer’s.
Woods: Because I’m guessing for the last 15 years, all research has followed in this hypothesis tailwinds and saying, “Ah, we’ve gotten closer.” So if we are going to find effective treatments, if we’re going to find a cure, we’ve got to keep going down this rabbit hole of the amyloid beta hypothesis. We’ve lost 15 years of time.
Sznycer-Taub: Absolutely. There are some people who will say that this hypothesis took all the funding that was out there and there was very little room for scientists who wanted to research any of the other causes. Remember, we still don’t actually know what causes Alzheimer’s, we don’t know what causes the memory loss. And this has, in some ways, kept other potential theories from receiving funding. And who knows, we could have seen curative or helpful pharmaceuticals that could have come out, had we been able to pursue some of these other theories.
Woods: Who’s going to jail for this? I’m kidding. We all probably watched the latest in the Theranos saga. I was a fan of the book, the podcast, obviously. Is this the next big series?
Hula: I don’t know if this is Theranos-level fraud, but it definitely could make a great documentary. And you’re right, how many billions of dollars? And I think more important than the dollars, Miriam, you said it, is how many years have we spent investigating this hypothesis and investigating this approach? There are a lot of others. There are metabolic approaches, anti-inflammatory approaches that have received not as much spotlight and not as much attention from scientists, from people who are funding this research that, like we said, could have.
Woods: Nick, what do you think those organizations are going to do next? What does this mean for life sciences and pharmaceuticals in a world where they have to, maybe this is hyperbolic, but start over?
Hula: I think this reminds us of one of the big dangers of over-funding in one area of research, putting all your eggs in one basket. I’m sure for certain diseases where we are very certain about the causes of disease and they approach we need to take, that might make sense.
But for a disease Alzheimer’s where we didn’t know, and at that point there were still questions about the amyloid hypothesis, even after the 2006 study, people still had trouble replicating it, which is the exact opposite of what science should be.
Woods: A hallmark of science is that you can replicate the results.
Hula: Exactly. It shows the dangers of overfunding in one area. But I think the second big impact on life sciences and why I think a lot of pharmaceutical manufacturers need to be thinking about, and a lot of other research organizations, is how do we prove the real world value of our therapies and our research moving forward? Because you look at different types of drugs that have come out that have used the amyloid approach. They have been, some have been FDA approved, we had Aduhelm, came out last year.