The Journal of Neuroscience has slapped expressions of concern on a pair of papers linked to the maker of a controversial drug to treat Alzheimer’s disease.
As we and others have reported, Cassava Sciences has been under intense scrutiny lately. In August, the law firm Labaton Sucharow – who is representing Cassava short sellers – submitted a “citizen’s petition” to the FDA regarding a regulatory filing from the company for its drug simulfilam and called on the agency to halt trials of the experimental medication because it had:
grave concerns about the quality and integrity of the laboratory-based studies surrounding this drug candidate and supporting the claims for its efficacy.
Last month, the Wall Street Journal reported that the company, which once boasted the sixth-best performing stock of 2021, has been under investigation by the Securities and Exchange Commission for questions about whether it provided manipulated data for simufilam.
At the center of the controversy, as we reported, are a slew of papers that constitute the backbone of Cassava’s regulatory finding (along with a grant application to the National Institutes of Health). The authors of those articles included Hoau-Yan Wang, of City University of New York (CUNY), and Lindsay Burns, a Cassava employee.
The two expressions of concern involve articles the Journal of Neuroscience published in 2009 and 2012, respectively titled “Dissociating β-Amyloid from α7 Nicotinic Acetylcholine Receptor by a Novel Therapeutic Agent, S 24795, Normalizes α7 Nicotinic Acetylcholine and NMDA Receptor Function in Alzheimer’s Disease Brain” and “Reducing Amyloid-Related Alzheimer’s Disease Pathogenesis by a Small Molecule Targeting Filamin A.” The papers have been cited 95 and 35 times, according to Clarivate Analytics’ Web of Science.
The notices are nearly identical but the one for the second article refers to an erratum which was reported on by WSJ last month:
The editors have been made aware of concerns about Western blots in this study, including those published with the article’s erratum (Wang et al., 2021). These and other concerns are currently under investigation by the academic authorities at the City University of New York (CUNY). JNeurosci will await the outcome of that investigation before taking further action
The journal’s move drew a mixed response on social media, where some users praised the action while others said it was long overdue. Elisabeth Bik, who has raised concerns about the papers on PubPeer, tweeted:
Another user noted that three more articles in the journal by Wang’s group have been flagged on PubPeer but haven’t received any official concern.
Last month, we reported that the journal Neuroscience was considering issuing an expression of concern – which it had drafted but not published – for one of Wang’s papers. Evidently, it’s still mulling.
Update, 0030 UTC, 12/20/21: Neuroscience has added an editorial note to the paper in question, which reads:
In response to allegations of data manipulation in an article published in Neuroscience Vol 135, Issue 1, 2005, Pages 247-261, and following COPE (Committee on Publication Ethics) guidelines, the journal asked the authors for images of the original, uncropped Western blots from this study. After careful examination of these original material, Neuroscience found no evidence of manipulation of the Western blot data or other figures of this publication. For transparency, the illustrations containing the uncropped Western blot images used for the assembly of these figures that were subjected to scrutiny can be found below. Any subsequent information arising from the institutional investigation will be considered once available.
That is followed by the images. Bik was unimpressed:
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If there is a manipulation of data why trials giving positive outcome for the drug? Are you supported or asked to contradict by anyone or do you have any vested interest in the shorts. Why didn’t you report that the trial, so far, have shown positive results?
Attempts to maintain market confidence in Cassava have alternated between “Ignore the evidence for shenanigans in the clinical trials, the fundamental research is sound!”, and “Ignore the evidence for shenanigans in the fundamental research, the clinical trials are above suspicion!”
That’s not what Retraction Watch does: it reports on retractions and expressions of concern.
I really wish there were some way to avoid having scientific research “cross the streams” with financial investing. It generally just makes an explosive mess. It is hard enough to find out the truth scientifically in the first place; it’s much harder when various parties have a financial incentive to obfuscate.