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The treatments surrounding Alzheimer's disease seem to be progressing and regressing.
Perhaps the most recent important development was the unanimous approval of Eli Lilly's new drug donanemab by an expert committee of experts from the U.S. Food and Drug Administration (FDA). As for the regression, it has to be mentioned that after two years of questioning and censorship in a landmark 2006 paper published in Nature, the authors finally publicly admitted to tampering with the images and agreed to retract the paper.
The most cited retraction of all time (more than 2,500 times in the past 18 years), which once claimed to identify specific targets for future drug development and once provided a precise window into the mechanisms of Alzheimer's disease, has become the target of criticism from peers two years ago, and is now fueling public distrust of scientific research and making us suspect that we may have misunderstood Alzheimer's disease in some way.
The amyloid hypothesis has struggled to translate into effective therapies
Since the 1990s, the field of Alzheimer's disease has been dominated by the so-called amyloid hypothesis. To put it simply: scientists have noticed that people with Alzheimer's disease have a lot of plaques in their brains, and they are mostly made up of amyloid. They hypothesized that this protein deposition could lead to uniquely damaging symptoms, and over time, patients would completely forget who they were and eventually die.
The retracted 2006 paper claimed to have identified the causative amyloid, theoretically providing a more specific target for future treatments.
For years, research and drug development have been targeting these amyloid plaques with the aim of eliminating them and thus slowing or even reversing the cognitive decline of patients. The problem, however, is that these efforts do not yield the desired results. Although significant advances have been made in the treatment of cancer and heart disease, Alzheimer's disease research has stalled.
The late Sharon Begley, a well-known American journalist and science writer, once revealed a kind of "institutional inertia" in which mainstream groups refute any alternative theories about the disease and suppress funding that might support innovative research.
Following Begley's observations, let's imagine: if we jump out of the so-called mainstream view, and use different theories and different methods to treat dementia, can we achieve a higher level of clinical improvement? There is still no answer to this question.
Should we pursue the ideal treatment at the same time?
As Science magazine pointed out when it reported on the retraction, scientists are still debating the correctness of the amyloid theory.
Opponents use the academic fraud incident as a basis to refute the traditional theory, arguing that it lacks a real breakthrough; Proponents point out that a variety of new drugs, including donelimab, have really improved some patients' conditions.
In 2019, Begley mentioned a failed drug, and that was aducanumab. It appears to be the embodiment of a flaw in the amyloid hypothesis, and its developer, Biogen, has halted clinical trials due to insufficient evidence of effectiveness and potentially dangerous side effects.
In 2021, adunamab triggered another crisis of confidence in Alzheimer's disease research.
With the help of the FDA's suspicious assistance and some statistical fraud, Biogen changed its stance: it allegedly found that a subset of patients appeared to have seen a slowdown in cognitive decline after taking aducanumab, so they decided to apply to the FDA for approval. The federal agency responsible for protecting patients from ineffective (or dangerous side effects) drugs agrees to the former's application. As a result, aducanumab was approved for marketing under the brand name "Aduhelm".
However, the first drug, which claims to slow the progression of Alzheimer's disease, has not only been unenthusiastically welcomed, but has also caused a huge stir. Feedback from doctors and nurses, as well as caregivers such as relatives and friends, has been negative; The benefits of the new drug seem insignificant, but the risks – especially the risk of severe intracerebral hemorrhage – are heart-wrenching.
In the years that followed, new drugs based on the same disease theory were introduced. They have slightly better clinical results, but safety concerns remain. Lecanemab (brand name Leqembi) was approved in 2023. At present, donemab is expected to be officially approved for marketing. There are many more drugs in development that appear to be effective in eliminating amyloid plaques, but clinical efficacy and safety are unclear.
Researchers estimate that 32 million people worldwide have Alzheimer's disease, 69 million have prodromal Alzheimer's disease, and 315 million people are in the preclinical stage of Alzheimer's, which together account for 22% of the population aged 50 years and older. In addition, the global trend of population aging is also accelerating the growth of the number of Alzheimer's patients.
The need for effective therapies is imminent. Of course, we should not choose one or the other, but solve the problem in a comprehensive and comprehensive way. Many scholars advocate for a radical change in the way Alzheimer's disease is handled. It's long overdue!
Sources:
Do we have Alzheimer’s disease all wrong?
Global estimates on the number of persons across the Alzheimer's disease continuum
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