Every step toward an effective Alzheimer’s treatment seems like another step back. It’s hard to feel like we’re running in place, as millions of patients and their families suffer from one of the most excruciating diseases known to humanity.
We went through those two steps again in the past two weeks when a groundbreaking study by federal scientific advisers was retracted. approval A new treatment. This treatment has led to modest clinical improvements for patients but comes with the same safety concerns that have dogged other recent drug candidates.
Author of the retracted paper in question, which was published the nature 2006 and claims to identify a specific target for future drug development, Agreed to withdraw their research entirelyAfter two years A fascinating investigation by science It was found that the original images were doctored.
The retraction adds to the crisis of confidence in scientific research as a whole, which my colleague Kelsey Piper has documented extensively. as science Note that Last week, there was Alzheimer’s research Among the most cited papers Over the past 18 years, nearly 2,500 citations have ever been withdrawn.
The 2006 paper appeared to be an important advance in our understanding of how Alzheimer’s works, providing precise mechanisms that underlie conventional theories of the disease.
But this was, we now know, a fraudulent invention. Instead, the withdrawal adds to nagging suspicions that we somehow misunderstand this most pernicious of predicaments.
The amyloid hypothesis has struggled to translate into effective treatments
After receiving the news, I decided to withdraw the nature paper, I thought of two people: Sharon BegleyMy former colleague at STAT who is sadly no longer with us, and Sarah Gilbert, daughter of a mother with Alzheimer’s with whom I became involved in the Alzheimer’s research debate three years ago.
I thought of Begley because of what he published in 2019 A meticulous investigation of the stagnant state of Alzheimer’s research Cut that core the nature Retracted results of the paper. Over the years, since the 1990s, the field has been dominated by the so-called amyloid hypothesis. To put it simply: Scientists have noticed that people with Alzheimer’s have a lot of plaques in their brains that are primarily made up of amyloid protein. They theorized that this build-up could be responsible for the uniquely devastating symptoms of Alzheimer’s, which over time would rob a person of their own identity and eventually lead to death. 2006 the nature The paper hypothesized to identify the exact amyloid protein in question, theoretically offering more specific targets for future therapies.
Research and drug development have been going on for years targeting those amyloid plaques and aiming to wipe them out, slowing or even reversing a person’s cognitive decline. The problem, as Begley documented, was that those efforts struggled to produce promising results. Even as science has made exciting advances in the treatment of cancer and heart disease, Alzheimer’s research remains stuck in the mud. His investigation reveals an institutional inertia that dismisses alternative theories of disease and cancels funding that might support out-of-the-box investigations.
Is it possible that a different approach to treating the disease could result in more impressive clinical improvements, as Begley’s story suggests? We don’t know yet. Last week, donanemab, which targets amyloid plaques, received a recommendation for FDA approval from the company’s scientific advisers, but it was Not an unqualified one.
as science mentioned His story in the retracted paperScientists are still debating whether the amyloid theory is valid. Skeptics cite fraudulent research and a lack of real progress; Supporters can point to this new class of drugs, including donanemeb, which have shown some improvement in some patients.
We need better strategies to find a cure for Alzheimer’s
In 2019, Begley mentioned a failed drug that seemed to epitomize the flaws in the amyloid hypothesis: aducanumab. Biogen, the drug’s developer, halted clinical trials due to scant evidence of its effectiveness and the risk of dangerous side effects.
Two years later, that same drug created another crisis of confidence in Alzheimer’s research.
Biogen, with dubious help from the FDA and some statistical skullduggery that I won’t bore you with, changed its position. It identified a subset of patients who experienced gradual cognitive decline while taking aducanumab and decided it was sufficient for FDA approval. The federal agency responsible for protecting patients from ineffective — or worse, dangerous — drugs agreed. And aducanumab, branded as Aduhelm, was approved.
But news of the first FDA-approved drug that claimed to slow the progression of Alzheimer’s disease, which you’d think would be greeted with joy, instead sparked a firestorm. These dubious methods used to justify its approval were criticized by doctors, nurses and others, including family and friends who cared for patients. The upside seemed marginal, while the risks — especially severe brain bleeding — were daunting.
I meet Sarah Gilbert to report on the fall of Aduhelm’s endorsement. His mother was recently diagnosed. And now he had to endure whiplash for promising a breakthrough treatment only to learn it was nothing of the sort.
“It was like pulling the rug out from under you because you wanted some hope,” he told me at the time.
In the years since, new drugs based on the same theory of disease have followed—with somewhat better clinical results but persistent safety concerns. Leqembi was approved in 2023. Donanemab has now received FDA approval. More medicine There are drugs in the pipeline that appear to be effective in eliminating amyloid plaques, but clinical efficacy and safety profiles are undetermined.
Any progress is welcome. Alzheimer’s disease affects approximately 6.7 million Americans and About 50 million May live with preclinical recurrences of the disease. So many people need help.
But as America’s population ages and the number of Alzheimer’s patients increases, we don’t need an either/or approach to finding a cure. We need all the above strategies. Researchers such as Carl Herap of the University of Pittsburgh argued For a fundamental overhaul of how we approach disease. It’s long overdue.
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