Alzheimer’s Research: Neuroscientist Alleges Irregularities

Nashville, United States – An American neuroscientist claims that some studies of the experimental agent simufilam (Cassava Sciences), a drug that targets beta-amyloid (Aβ) in Alzheimer’s disease (AD), are flawed, and has therefore shared his concerns at the National Institutes of Health (NIH).

Amyloid accumulation as a main line of research: wrong bases?

the Dr. Matthew SchragPhD, from the department of neurology at Vanderbilt University Medical Center, Nashville, Tennessee, found what he calls inconsistencies in major studies looking at the drug.

In a whistleblower report to the NIH about the drug, Dr. Schrag says several prominent researchers have altered images and reused them for years to support the hypothesis that amyloid buildup in the brain causes the MY. The NIH has funded research into Aβ as a potential cause of AD to the tune of millions of dollars for years.

“This hypothesis [l’accumulation d’amyloïde] has been the dominant line of research in this area,” Dr. Schrag told Medscape Medical News. “Many of the therapies that have been developed and clinically tested over the past decade have focused on the amyloid hypothesis in one formulation or another. So this is an important part of how we look at Alzheimer’s disease,” he added.

In an in-depth article published in Science on July 22 and written by the investigative journalist Charles PillerDr. Schrag said he got involved after a colleague suggested he work with a lawyer who was investigating simufilam [1]. The attorney paid $18,000 to Dr. Schrag to investigate the search for the agent. Cassava Sciences denies any wrongdoing, according to the article.

Dr. Schrag has run many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of protein in a sample – that appeared to have been altered.

Important issues

Dr. Schrag found “apparently altered or duplicated images in dozens of newspaper articles,” the article says. Science [1].

“The stakes are high and it is also important to recognize the limits of what we can do. We’ve worked with what’s been published, what’s publicly available, and I think that should alert us, but we haven’t looked at the original material either because it’s just not available to us “said Matthew Schrag to Medscape Medical News.

However, he added that, despite these limitations, he believes “the elements are important enough for regulators to take a closer look at them to make sure the data is correct.”

The magazine Science reports that it has launched its own independent review, asking several neuroscience experts to review the research as well. They agreed with Matthew Schrag’s general conclusions that something was wrong.

Many of the studies implicated in the whistleblower report involve Sylvain Lesne, PhD, who directs the Lesné lab at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague the Dr. Karen Ashe, PhD, professor of neurology at the same institution, is also mentioned in the whistleblower report. She is co-author of a report published in 2006 in Nature which identifies an Aβ subtype as a potential culprit of AD.

Medscape Medical News contacted Sylvain Lesné and Karen Ashe for comment, but did not receive a response.

However, an email from a spokesperson for the University of Minnesota said the institution is “aware that questions have been raised regarding certain images used in peer-reviewed research publications authored by faculty at Karen Ashe and Sylvain Lesné University. The University will follow its protocols for reviewing issues raised by complaints. At this time, we have no further information to provide. »

Invited to comment, Maria CarrilloPhD, scientific officer of the Alzheimer’s Association, told Medscape Medical News that if the “accusations of tampering with images or data are true, all those responsible must be held accountable – including scientists, their institutions, journals and funders”.

Accountability would include admission of tampering, retraction of tampered images or data, reimbursement of funds and ineligibility of future funding for those found responsible, as well as new or stricter enforcement of policies to prevent the repetition of these frauds, she added.

A matter of trust

Matthew Schrag underlined “the important relationship of trust between patients, doctors and scientists when we explore diseases for which we do not have good treatments”. He added that when patients agree to participate in trials and take the associated risks, “we owe them a very high degree of integrity when it comes to basic data. »

Maria Carrillo nods. “Progress in the diagnosis, risk reduction, treatment and prevention of Alzheimer’s disease and all dementias is truly urgent, but there is no room for shortcuts based on dishonesty and deception,” she said. “We owe this to everyone who has been touched by Alzheimer’s disease, those affected, their families, those at risk, research participants, and the medical and research community. »

Matthew Schrag also pointed out that resources to study these diseases are limited. “It is possible that these resources are misdirected. It is important that we pay attention to data integrity issues, to ensure that we are investing in the right places. »

The term “fraud” does not appear in Matthew Schrag’s whistleblower report, nor does he cry foul. However, his work has prompted an ongoing independent investigation into allegations by several journals that have published the work in question, including Nature and Science Signaling.

Matthew Schrag said that if his conclusions were validated by an investigation, he would like the scientific data to be corrected.

“Ultimately, I would like to see a new set of hypotheses emerge that allows us to look at this disease from a new angle,” he added.

“As we continue to move forward, it is important to note that this survey addresses only a small segment of Alzheimer’s disease and dementia research and does not reflect the full science in this area,” said Maria Carrillo.

Potential treatments that span the full biology of Alzheimer’s disease are advancing, she added. “Future treatments will need to address amyloid, tau, and neurodegeneration, as well as other brain changes that play a role in the disease. »

Matthew Schrag notes that the work described in the article by Science were made outside of his work at Vanderbilt University Medical Center and that his views do not necessarily represent those of Vanderbilt University or Vanderbilt University Medical Center.

The article was originally published on under the title Neuroscientist Alleges Irregularities in Alzheimer’s Research. Translated by Stephanie Lavaud.

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