The drug in question, simufilam, is not approved anywhere, but the scandal could undermine public confidence.
Alzheimer’s disease is the most common form of dementia, and with a rapidly aging global population, it is fueling unprecedented demand for expensive patient care. There have been an estimated 400 clinical studies since the first trial of Alzheimer’s drugs in 1987.
The demand for treatment solutions, however, is not without significant risks. There have been recent allegations that the research underpinning widespread knowledge about what causes Alzheimer’s may be fraudulent. The impact of this on clinical trials is a potentially huge blow to people living with Alzheimer’s and their caregivers.
In this case, it might be an exaggeration to say that all Alzheimer’s research is now compromised. But the allegations may lead us to question whether the governing bodies of drug research and approval are really effective.
An important report by Charles Piller @cpiller that puts the spotlight on research integrity in Alzheimer’s research. https://t.co/8a6bwxyahF
— Matthew Schrag (@schrag_matthew) July 21, 2022
A potentially wrong assumption
Concerns about possible fraud in Alzheimer’s research follow findings by neurologist and physician Matthew Schrag, detailed in the journal Science.
Schrag wrote that an ongoing Alzheimer’s trial investigating the experimental drug simufilam was based on doctored images published by scientists years earlier. If true, patient volunteers in drug trials, including simufilam studies, may be facing unnecessary health risks associated with the experimental treatment, likely without any hope of clinical benefit.
In addition, years of drug development costing tens of millions of dollars could have been lost. The fundamental premise of what causes brain cell death in Alzheimer’s, and by extension what kind of drugs to develop for treatment, may now need reconsideration.
Some contemporary Alzheimer’s clinical trials are based on a now potentially flawed hypothesis: that brain cell death is triggered by the early formation in the fluid that bathes the brain of small clumps of proteins called amyloid oligomers.
A highly influential and widely cited study is at the center of the current controversy. The authors stated that mouse models of Alzheimer’s showed that memory impairment was associated with the accumulation of amyloid oligomers. Schrag found compelling evidence that the image presented in the 2006 paper may have been altered.
But what about peer review?
The internationally adopted peer review system, where experts in the discipline anonymously review scientific data submitted for publication, usually ensures robust results. This should reassure the public about a study’s scientific claims. However, as the saying goes, science doesn’t lie, but people do.
In this case, Schrag reviewed imagery scores in scientific papers written by neuroscientist Sylvain Lesné and suggested that significant imagery alteration had occurred. Leading independent image analysts and internationally recognized Alzheimer’s researchers supported Schrag’s claims.
Neuroscientists may be sorely disappointed. Publications that changed what we know about Alzheimer’s or other diseases now appear based on manipulated data. It potentially discredits neuroscientists and undermines public trust.
The allegations have brought trials for two simfilam drugs under serious scrutiny.
Importantly, simufilam has not been approved by any regulatory agency. But a recent US Food and Drug Administration (FDA) approval of the drug aducanumab, against expert advice that warned there wasn’t enough evidence to show it worked, has doctors treating people with Alzheimer’s are more sensitive.
Other avenues of research
So does the news of this possible fraud mean that the field of Alzheimer’s research is corrupt? Can we be sure that what patients are being prescribed is safe and working?
We need to consider the larger context that publication of incorrect data is rare and research misconduct is even rarer. If incorrect data is identified, restorative practices are usually swift and thorough, including the publication of “errata” corrections or, possibly, a retraction of the findings by scientific journals. Significant penalties are also imposed for willful misconduct in the investigation.
In addition, there are multiple clinical trials looking at multiple aspects of the complex Alzheimer’s cascade, from what causes the disease to how it affects memory and thinking. These are based on credible scientific findings.
The elimination of amyloid oligomers, which is now being questioned, is just one avenue that scientists have pursued.
The vast majority of scientists are doing the right thing all the time, and if regulatory approval authorities, such as our Therapeutic Goods Administration and the FDA, continue to reasonably and thoroughly scrutinize the evidence provided for approval, then we can hope for a better future for people. living with Alzheimer’s.
John Mamo, John Curtin Distinguished Professor of Health Sciences, Director, Curtin Health Innovation Research Institute, Curtin University
This article is republished from The Conversation under a Creative Commons license. Read the original article.