Experimental Stroke Drug Faces Scrutiny Following Allegations of Misconduct and Increased Deaths
A groundbreaking experimental drug designed to limit brain damage after strokes is facing intense scrutiny after allegations of misconduct and a concerning rise in deaths. The US National Institutes of Health (NIH) had invested up to $30 million in the study of a compound called 3K3A-APC, which aimed to help individuals shortly after experiencing an acute ischemic stroke. This condition occurs when a clot obstructs blood flow to a part of the brain. The decision to support this drug seemed justified, as previous lab studies, mainly conducted by respected neuroscientist Berislav Zlokovic from the University of Southern California (USC), had generated promising data.
The primary goal of scientists has been to reduce brain cell death, bleeding, and inflammation that occur after a stroke. These consequences are often a result of the disruption of the blood-brain barrier, a network of small blood vessels that deliver oxygen and nutrients while protecting the brain from harmful substances. While the only approved stroke drug, tPA, effectively clears blockages and reduces death and disability, it also carries the risk of dangerous brain bleeding. 3K3A-APC was believed to have the potential to mitigate such damage and prevent brain cell death, according to ZZ Biotech, the developer of the experimental drug.
However, a recently obtained 113-page dossier, submitted to the NIH by a group of whistleblowers, presents a less encouraging perspective. The dossier focuses on evidence from a phase 2 trial suggesting that the experimental drug may have actually contributed to an increase in deaths during the first week of treatment. Out of the 66 stroke patients who received 3K3A-APC, six died within this period, compared to just one among the 44 participants in the placebo group. Although the death rate evened out after a month, patients who received the drug also exhibited a higher tendency toward greater disability and dependency 90 days post-treatment, according to the trial results.
The dossier raises further concerns by highlighting apparent misconduct in dozens of papers from Zlokovic’s lab. The papers, many of which supported the idea that the compound was ready for human testing, contain potentially modified data that appears to favor the scientist’s hypotheses. These hypotheses revolve around the blood-brain barrier’s role in stroke and Alzheimer’s disease, as well as the supposed impact of 3K3A-APC on it.
Four former members of Zlokovic’s lab, speaking anonymously to Science, confirm the anomalies identified by the whistleblowers and attest to a culture of intimidation within the lab. They claim that Zlokovic frequently pressured them and others to manipulate data to fit desired results. In some instances, he allegedly instructed individuals to alter lab notebooks after experiments were completed to ensure they only contained the expected outcomes. These testimonies shed light on a concerning environment that could compromise the integrity of the research.
The revelations surrounding the experimental stroke drug and the alleged misconduct within Zlokovic’s lab raise significant questions about the reliability and safety of 3K3A-APC. The conflicting outcomes of the phase 2 trial and the apparent manipulation of data cast doubt on the drug’s efficacy and the validity of supporting research. As the NIH investigates these allegations, it is crucial to strike a balance between the potential benefits of experimental treatments and the ethicality of the scientific process.
Overall, the controversy surrounding the experimental stroke drug underscores the importance of maintaining rigorous standards in scientific research and ensuring transparency for the sake of patient safety and public trust. The scrutiny faced by 3K3A-APC serves as a reminder that thorough evaluation, unbiased reporting of results, and adherence to ethical practices remain paramount in the pursuit of medical advancements.
