Research on Alzheimer’s disease: suspicions of scientific misconduct

3D computer-generated image representing amyloid plaques (brown) in the brain, which kill surrounding neurons (blue).  Large numbers of plaques are characteristic of Alzheimer's disease.

Alzheimer’s disease, which affects 50 million people worldwide, is a major public health issue. But despite intense research efforts for decades, no drug that could slow its progression is yet available. Could it be because some of the research leads are paved with fraudulent work?

This is what a survey of the journal suggests Science, published on July 22, which followed in the footsteps of an American researcher from Vanderbilt University (Nashville, Tennessee), Matthew Schrag. The investigations of this neuroscientist and neurologist began in an atmosphere of American thriller: a law firm contacted him to examine the work concerning simufilam, an anti-Alzheimer’s drug developed by the American laboratory Cassava Sciences. This small molecule would improve cognitive functions by stabilizing a protein, filamin A, thus helping to stabilize various proteins in the brain, including β-amyloid peptides, emblematic of the disease.

The lawyers were mandated by researchers with small shares of Cassava Sciences, who feared fraud on this research. By looking at the scientific literature emanating from the company and associated researchers, independently of his own university and hospital supervision, Matthew Schrag was quick to identify possible manipulations, relating to scientific images and digital data.

The simufilam in question

His findings – paid for $18,000 by the law firm – fueled a claim to the US drug agency, the Food and Drug Administration (FDA) in August 2021, asking it to halt two clinical trials of simufilam . The letter invoked “multiple reasons to question the quality and integrity of the work underlying its administration in Alzheimer’s disease”. The FDA denied this request.

Since then, numerous articles by Hoau-Yan Wang (City University of New York, CUNY), adviser to Cassava, and Lindsay Burns, vice president of the company, who had co-discovered the target of the simufilam, have been combed through. . This review has already resulted in corrections, reader alerts – “expressions of concern” – from the scientific journals that published them, or even outright retractions.

The PubPeer site, where questions can be raised publicly about the quality of scientific work, reports comments and criticisms on 33 articles signed by Hoau-Yan Wang. One of these publications, retracted, was carried out in collaboration with French researchers, some of whom belong to the Servier International Research Institute. Matthew Schrag, reports Sciencefor its part, compiled a file of 34 articles by researchers in connection with Cassava raising “serious concerns of scientific misconduct”. He recently sent it to the National Institutes of Health (NIH), which funded the offending work to the tune of tens of millions of dollars. If fraud were proven, he could receive a share of the sums reimbursed as a reward for this report. Cassava chairman Remi Barbier, who is also Lindsay Burns’ husband, denies all allegations, says Science.

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