Alzheimer’s disease affects about 50 million people worldwide. Untreated patients for whom scientific investigation of disease mechanisms is critical. According to a recent investigation by the journal Science, several studies have been the subject of fraud and manipulation. Discoveries made after six months of research after the revelations by neurologist Matthew Schrag of Vanderbilt University (USA).
Possible fakes in a large study
The questions are based on the work of the Frenchman Sylvain Lesnay, published in 2006. Then, after earning his PhD in American research, he published a paper in Nature about Aβ*56, an oligomeric protein that can cause memory problems after injection. to the rats. Work that goes in the direction of other studies published at the time: Alzheimer’s disease occurs due to the accumulation of β-amyloid proteins aggregated in plaques between neurons.
“Sylvain Lesnay’s contribution was to find out in which form the peptides are most toxic and to show that cognition changes with plaque accumulation, which is easy to measure in rodents. In soluble form, β-amyloids are less dangerous. mainly accumulate in oligomers that have an effect on the patient,” explains Professor Philippe Amouiel, CEO of the Alzheimer’s Foundation at Sciences et Avenir.
This major Alzheimer’s study has been cited over 2,200 times in the scientific literature. But according to Science, several images from that study have been altered. “After analyzing the images, it was shown that in the scientific article by Sylvain Lesnay, some of them look very similar and are 97% similar. Looking at other published studies, it seems that the same image is being used,” Philippe Amouiel explains. . In total, more than 20 suspicious items were identified.
What’s more, the results of a large 2006 study published in the journal Nature have never been replicated, which is usually a prerequisite for proving the reliability of a study. “Today in sciencehalf of the results are never confirmed,” says Philippe Amouiel. “On the one hand, there are conscientious people who will publish an artifact by mistake (an error that occurred during manipulations – ed.) without their knowledge. Or, following the logic of “publish or perish” (the pressure under which researchers are forced to publish scientific papers at any cost in order to continue their careers, editor’s note), researchers are forced to do things that violate the very principle of scientific publication, that is, say, to publish reliable and verified information.”
Simufilam, a drug to be taken off the market?
Another embarrassing moment raised by the journal Science: work on simufilam, a drug for Alzheimer’s disease developed in the laboratory of Cassava Sciences and based precisely on the idea that we are talking about β-amyloids. A topic on which the law firm contacted Matthew Shrag to examine the research being done around this molecule.
According to the laboratory, simufilam has the property of stabilizing a protein (filamin A), which may contribute to the stabilization of several proteins in the brain, including β-amyloids. In the United States, a petition was filed with the FDA (Food and Drug Administration responsible for drug marketing validation) denouncing the fact that these results were only proven in laboratory studies of cassava. “Despite requests to stop clinical trials, those that have been started are still ongoing. The FDA has said it wants to conduct an investigation to see if the drug should be withdrawn from the market,” said Prof Amouyel.
Aducanumab ‘moved forward’ despite criticism
In 2021, the US marketing of aducanumab has already made people cringe. This molecule, which does not cure Alzheimer’s disease, but acts on one of these processes, is intended to treat the early stages of the disease. The active substance of aducanumab is an anti-amyloid monoclonal antibody that targets soluble and insoluble forms of amyloid peptides, stopping or reducing the clinical signs of dementia.
However, clinical trials conducted with this drug have shown mixed results. “The drug was approved despite the negative opinion of the scientific committee of the FDA. In my opinion, he was pushed forward no matter what because there is tremendous pressure to find an answer to Alzheimer’s, not because the results he showed were scientifically sound. “explains Science et Avenir Brice Wissel, Professor neuroscience at the University of New South Wales and protein controversy specialist β-amyloids.
15 years of research for nothing?
After these discoveries, the world of Alzheimer’s disease research has been shaken for days. But research since 2006 has not been undermined. “The story doesn’t collapse,” explains Prof. Amouiel, who, along with Prof. Wissel, believes that the science behind the disease simply goes far beyond a single theory of β-amyloid proteins.
The role of immunity, lipids, tau protein – all this has yet to be studied in parallel with the theory of protein plaques. “Blocking or suppressing amyloid-beta is probably not the only response to Alzheimer’s disease. It is always possible that drugs developed in this direction will be effective. Let’s wait and see the results. adds Professor Wissel.
So the search was not in vain. And the study of Science always leaves the door open to doubt. Matthew Schrag and the journal were asked to work with the raw data used in the studies in question to try to replicate the findings. But at the moment, no one has given consent to their transfer.