Whistleblowers and former lab members suggest star neuroscientist Berislav Zlokovic may have manipulated data that support a major stroke trial and important Alzheimer’s research

In 2022, the U.S. National Institutes of Health (NIH) placed a large bet on an experimental drug developed to limit brain damage after strokes. The agency committed up to $30 million to administer a compound called 3K3A-APC in a study of 1400 people shortly after they experience an acute ischemic stroke, a perilous condition in which a clot blocks blood flow to part of the brain.

The gamble seemed warranted. Lab studies, most by a longtime grantee, prominent University of Southern California (USC) neuroscientist Berislav Zlokovic, had generated promising data...

...For many years, scientists have tried to reduce the brain cell death, bleeding, and inflammation that can follow a stroke, some of which results from disruption of the blood-brain barrier—a system of tiny blood vessels that delivers oxygen and nutrients but shields the brain from toxic substances. tPA, the only approved stroke drug in the United States and Europe, can vastly reduce death and disability by clearing a stroke’s blockage, but the drug, too, can cause dangerous brain bleeding. 3K3A-APC could help mitigate such damage and prevent brain cells from dying, ZZ Biotech said...

... But a 113-page dossier obtained by Science from a small group of whistleblowers paints a less encouraging picture. The dossier, which they submitted to NIH, highlights evidence from the phase 2 trial that the experimental remedy might have actually increased deaths in the first week after treatment: Six of the 66 stroke patients who received 3K3A-APC died within this period, compared with one among 44 in the placebo group, although the death rate evened out after a month. Patients who received the drug also trended toward greater disability and dependency at the end of the trial, 90 days after treatment.

Deepening the concern, the dossier also highlights evidence that dozens of papers from Zlokovic’s lab—including many supporting the idea that the compound was ready for human testing—contain seemingly doctored data that suggest scientific misconduct. The whistleblowers say apparent changes to images used for protein identification and other purposes seem to skew results in favor of the scientist’s hypotheses, which include influential ideas about the blood-brain barrier and its role in stroke and Alzheimer’s disease, as well as how 3K3A-APC supposedly affects it...

...But speaking to Science anonymously, four former members of Zlokovic’s lab say the anomalies the whistleblowers found are no accident. They describe a culture of intimidation, in which he regularly pushed them and others in the lab to adjust data. Two of them said he sometimes had people change lab notebooks after experiments were completed to ensure they only contained the desired results. “There were clear examples of him instructing people to manipulate data to fit the hypothesis,” one of the lab members says...