FDA-passed Parkinson’s Drug Part of Falsified Research Probe
An investigational Parkinson’s drug under development by Prothena is being called into question because of falsified research publication allegations centered around one of NIH’s top officials. An investigation by the journal Science raises issues with research conducted and published over the past two decades by NIH neuroscientist Eliezer Masliah. As Science was unveiling its findings from a two-year probe 9/26, NIH simultaneously released a statement saying that following its investigation, it had “made findings of research misconduct” against Masliah for “falsification and/or fabrication involving re-use and relabel of figure panels” in two publications.
Science says its investigation questions significantly more studies than the two cited in NIH’s statement. Forensic scientific analysts assisting Science produced a 300-page dossier that documented a steady stream of suspect images between 1997 and 2023 in 132 of Masliah’s published research papers. It also found that “scores of his lab studies” are “riddled with apparently falsified Western blots — images used to show the presence of proteins—and micrographs of brain tissue. Numerous images seem to have been inappropriately reused within and across papers, sometimes published years apart in different journals, describing divergent experimental conditions.”
The journal says Masliah’s work helped gain a research nod from FDA for clinical trials of Prothena’s Parkinson’s drug prasinezumab, which is intended to attack alpha-synuclein, whose build-up in the brain has been linked to the condition’s debilitating physical and cognitive symptoms. Prasinezumab is currently being evaluated in the Phase 2b PADOVA study, the company says, and an ongoing long-term extension of Phase 2 PASADENA study. Both studies are being conducted by Roche, its development partner.
Science says that a trial of 316 Parkinson’s patients, reported in 2022 in The New England Journal of Medicine, showed that prasinezumab had no benefit compared to a placebo. “And volunteers given infusions of the antibody suffered from far more side effects such as nausea and headaches than those in a placebo group who received sham infusions,” it says. “Prothena is now collaborating in another trial of the drug candidate involving 586 Parkinson’s patients.”
The forensic dossier also questions some of Masliah’s earliest work on alpha-synuclein, “raising further doubts about the foundations of Prothena’s drug,” Science says. “A seminal 2000 Masliah article in Science, for example, suggested alpha-synuclein might kill certain brain cells and speed the development of brain deposits called Lewy bodies that are hallmarks of Parkinson’s and are often seen in Alzheimer’s patients. But the paper contains an apparently doctored image and another image the dossier authors deemed questionable.”
University of Florida neurologist Michael Okun told Science that a “single nonreplicable finding is in itself not worrisome,” but it raises greater concern in light of “convincing evidence of spliced and cloned images which appeared frequently in the decades following.” He said it is “deeply troubling” that FDA approved human trials of prasinezumab based largely on suspect papers from Masliah’s lab. The agency declined Science’s request for comment on the prasinezumab findings challenged within the dossier.