Two decades of Alzheimer's research may be based on deliberate fraud that has cost millions of lives
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.
…
After reviewing the images, molecular biologist Elisabeth Bik said of the paper, “The obtained experimental results might not have been the desired results, and that data might have been changed to … better fit a hypothesis.”
Should this fraud turn out to be as extensive as it appears at first glance, the implications go well beyond just misdirecting tens of billions in funding and millions of hours of research over the last two decades. Since that 2006 publication, the presence or absence of this specific amyloid has often been treated as diagnostic of Alzheimer’s. Meaning that patients who did die from Alzheimer's may have been misdiagnosed as having something else. Those whose dementia came from other causes may have falsely been dragged under the Alzheimer’s umbrella. And every possible kind of study, whether it's as exotic as light therapy or long-running as nuns doing crossword puzzles, may have ultimately had results that were measured against a false yardstick.
In the face of the potential fraud unearthed by Schrag, it’s not as if the world has changed overnight.
Four months after Schrag submitted his concerns to the NIH, the NIH turned around and awarded Lesné a five-year grant to study … Alzheimer’s. That grant was awarded by Austin Yang, program director at the NIH’s National Institute on Aging. Yang also happens to be another of the co-authors on the 2006 paper.
Science has carefully detailed the work done in the analysis of the images. Other researchers, including a 2008 paper from Harvard, have noted that Aβ56 is unstable and there seems to be no sign of this substance in human tissues, making its targeting literally worse than useless. However, Lesné claims to have a method for measuring Aβ56 and other oligomers in brain cells that has served as the basis of a series of additional papers, all of which are now in doubt.
There seems to be no doubt that oligomers may play a role in cognitive impairment. However, that role may not be nearly as direct, or as significant, as the 2006 paper and subsequent papers by Lesné have suggested. It’s quite possible that the specific oligomer Aβ*56 may not even exist outside of Ashe’s transgenic mice.
And it seems highly likely that for the last 16 years, most research on Alzheimer’s and most new drugs entering trials have been based on a paper that, at best, modified the results of its findings to make them appear more conclusive, and at worst is an outright fraud.
(read moar)
https://www.dailykos.com/stories/2022/7/22/2111914/-Two-decades-of-Alzheimer-s-research-may-be-based-on-deliberate-fraud-that-has-cost-millions-of-lives