Two decades of Alzheimer’s research was based on deliberate fraud by 2 scientists that has cost bill
Last month, drug company Genentech reported on the first clinical trials of the drug crenezumab, a drug targeting amyloid proteins that form sticky plaques in the brains of Alzheimer’s disease patients. The drug had been particularly effective in animal models, and the trial results were eagerly awaited as one of the most promising treatments in years. It did not work. “Crenezumab did not slow or prevent cognitive decline” in people with a predisposition toward Alzheimer’s.
Last year, the Food and Drug Administration (FDA) narrowly approved the use of Aduhelm, a new drug from Biogen that the company has priced so highly that it’s expected to drive up the price of Medicare for everyone in America, even those who never need this drug. Aduhelm was the first drug to be approved that fights the accumulation of those “amyloid plaques” in the brain. What makes the approval of the $56,000-a-dose drug so controversial is that while it does decrease plaques, it doesn’t actually slow Alzheimer’s. In fact, clinical trials were suspended in 2019 after the treatment showed “no clinical benefits.” (Which did not keep Biogen from seeking the drug’s approval or pricing it astronomically.)
Over the last two decades, Alzheimer’s drugs have been notable mostly for having a 99% failure rate in human trials. It’s not unusual for drugs that are effective in vitro and in animal models to turn out to be less than successful when used in humans, but Alzheimer’s has a record that makes the batting average in other areas look like Hall of Fame material.
And now we have a good idea of why. Because it looks like the original paper that established the amyloid plaque model as the foundation of Alzheimer’s research over the last 16 years might not just be wrong, but a deliberate fraud.
The suspicion that something was more than a little wrong with the model that is getting almost all Alzheimer’s research funding ($1.6 billion in the last year alone) began with a fight over the drug Simufilam. The drug was being pushed into trials by its manufacturer, Cassava Sciences, but a group of scientists who reviewed the drug maker’s claims about Simufilam believed that it was exaggerating the potential. So they did what any reasonable person would do: They purchased short sell positions in Cassava Sciences stock, filed a letter with the FDA calling for a review before allowing the drug to go to trial, and hired an investigator to provide some support for this position.
As Science reports, it was that investigator, Vanderbilt University neuroscientist and junior professor Matthew Schrag, who tipped over the whole applecart to discover that it wasn’t just that Cassava’s drug was ineffective. There’s good evidence that for the last 16 years, almost everyone has had the wrong idea about the cause of Alzheimer’s. Because of a fraud.
In 2006, Nature published a paper titled “A specific amyloid-β protein assembly in the brain impairs memory.” Using a series of studies in mice, the paper concluded that “memory deficits in middle-aged mice” were directed caused by accumulations of a soluble substance called “Aβ*56.” This was a specific form of a group known as “toxic oligomers” that had long been suspected as the possible precursors of amyloid plaques. The paper then went on to directly connect that condition to “cognitive deficits associated with Alzheimer’s disease” independently of other conditions affecting the aging brain.