Fraud in Stroke and Alzheimer’s Disease Drug Trials—Again?

Whistleblowers detect data and images in published papers that appear to have been manipulated, according to Science magazine

University of California superstar neuroscientist Berislav Zlokovic is now in the spotlight every science star hopes to avoid: Whistleblowers charge that “dozens” of published papers from Zlokovic’s lab contain “seemingly doctored data that suggest scientific misconduct,” according to a report in Science magazine. (1)

The compound under investigation in many of these published reports, 3K3A-APC, seemed a “promising” stroke treatment in laboratory studies. Subsequently, a 1400-person safety trial was also found to be promising; the safety trial was sponsored by a company co-founded by Zlokovic, ZZ Biotech.

The compound 3K3A-APC is thought to affect the blood-brain barrier, where blood clots can form, causing stroke and stopping blood flow into and out of the brain. Currently, the most frequently used treatment for acute ischemic stroke is the “clot-busting” drug tissue plasminogen activator or tPA. However, tPA can also cause post-stroke bleeding, which kills brain cells. It’s hypothesized that 3K3A-APC “mitigates” the excess bleeding that tPA can cause. (1)

Zlokovic also sees a role for 3K3A-APC in treating Alzheimer’s disease: His lab has published papers showing that the compound “helps” move beta-amyloid proteins out of the brain via the blood-brain barrier. (1)

AUTHOR’S NOTE: Not all neuroscientists agree that beta-amyloid proteins cause or even contribute to Alzheimer’s disease, and a number of compounds that claim to remove beta-amyloids from the brain have had no positive effects on Alzheimer’s disease progression. (2)

Following the apparently successful safety trial, the National Institutes of Health (NIH) invested $30M in a Phase 2 trial of 3K3A-APC in people who’d had acute ischemic stroke. The compound appeared to prevent the “tiny, asymptomatic brain hemorrhages” that can occur after stroke victims are treated with tPA, surgery, or both. (1)

Following a precedent established for drugs developed to treat AIDS, the Food and Drug Administration (FDA) granted “fast track” status to 3K3A-APC, setting it up to receive “accelerated approval,” according to Charles Piller in Science. (1)

Enter the whistleblowers.

Fair warning: This post is a fragment, a tease, because this story deserves a deep dive into just how much fraud is occurring in the basic science that allows—or disallows—drug development that eventually results in medications prescribed to millions.

Meanwhile, back to the whistleblowers, who came to a different conclusion about the success of the Phase 2 trial than that reported to NIH. Their 113-page dossier showed that patients treated with 3K3A-APC had a worse outcome in the first week than patients given placebo.

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 depen-
dency at the end of the trial, 90 days after treatment. (1)

Doctored data, manipulated images, obscured results from clinical trials—what is going on in neuroscience research?

In July 2023, Stanford University President and neuroscientist Marc Tessier-Lavigne resigned after his Alzheimer’s disease research “fell below customary standards of scientific rigor and process.” (2)

You can read my SubStack post about the Stanford University misconduct case
here. (2)

On November 15, 2023, Medpage Today reported the clinical trial failure of another Alzheimer’s disease drug, Gantenerumab, which targets the amyloid plaques found in the brains of people with Alzheimer’s disease. (3)

Randall Bateman, MD (Washington University School of Medicine, St. Louis), told Medpage Today, “Gantenerumab didn’t fully remove amyloid plaques in most patients and didn’t substantially improve cognitive or clinical decline at the doses used.” (3)

You can read a more detailed explanation of why this new Alzheimer’s disease drug failed here.

The neurologic symptoms and damage in ME/CFS—and, as we’re learning, both Covid-19 and Long Covid—are significant and call out for serious, immediate research into cause and treatment. If neuroscience has become rife with misconduct, where are patients and clinicians to turn?

BIBLIOGRAPHY
1.     Charles Piller. “BRAIN GAMES? 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.” Science, November 13, 2023. https://www.science.org/content/article/misconduct-concerns-possible-drug-risks-should-stop-stroke-trial-whistleblowers-say
2.     Neenyah Ostrom. “What’s Gone Wrong in Alzheimer’s Disease Research? Published research once again found to contain fudged images—can any neuroscience research be trusted?” July 20, 2023. Chronic Illness and HHV-6 Report, SubStack. https://immuneillnessreport.substack.com/p/whats-gone-wrong-in-alzheimers-disease
3.     Sophie Putka. “Gantenerumab Failed to Slow Cognitive Decline in Early Alzheimer's—Amyloid plaque levels went down, but not enough for clinical benefit.” November 15, 2023. Medpage Today.
https://www.medpagetoday.com/neurology/alzheimersdisease/107385?xid=nl_mpt_DHE_2023-11-15&eun=g2191631d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%20Evening%202023-11-15&utm_term=NL_Daily_DHE_dual-gmail-definition

ABOUT THE AUTHOR
Neenyah Ostrom was the first reporter in the United States to report weekly for a decade on ME/CFS. Her reporting on the Chronic Fatigue Syn­drome epidemic from 1988-1997 is getting increased atten­tion thanks to Robert F. Kennedy Jr.  He discusses her work exten­sively in his 2022 best seller, The Real Anthony Fauci. Ostrom’s groundbreaking reporting on Chronic Fatigue Syn­drome and AIDS appeared in the New York Native from 1988 to 1997.

Ostrom wrote the Foreword to the recently published THE REAL AIDS EPIDEMIC: How the Tragic HIV Mistake Threatens Us All by Rebecca Culshaw, Ph.D.

Ostrom is the author of four books about the Chronic Fatigue Syndrome epidemic: What Really Killed Gilda Radner? Frontline Reports On The Chronic Fatigue Syndrome Epidemic (1991; TNM Inc., New York, NY), 50 Things Everyone Should Know About The Chronic Fatigue Syndrome Epidemic And Its Link To AIDS (1992; TNM Inc. and St. Martin’s Press, New York, NY; published in Japanese by Shindan-to-Chiryo, 1993; and in French by Les Edi­tions Logiques, 1994), and America’s Biggest Cover-Up: 50 More Things Everyone Should Know About The Chronic Fatigue Syn­drome Epidemic And Its Link To AIDS (1993; TNM Inc., New York, NY); and America’s Biggest Cover-Up: 50 More Things Everyone Should Know About The Chronic Fatigue Syn­drome Epidemic And Its Link To AIDS, Updated 2^nd Edition(2022, available as a Kindle ebook and paperback on Amazon.com). Her most recent book, Ampligen: The Battle for a Promising ME/CFS Drug (2022) is available as a Kindle ebook and paperback on Amazon.com

 In 1995, Ostrom and New York Native were rec­ognized as having reported one of the top 25 most-censored stories in the U.S. press by 1995’s Censored: The News That Didn’t Make The News And Why (The 1995 Project Censored Yearbook by Sonoma State University Professor Carl Jensen, introduction by Michael Crichton; pub­lished by Four Walls Eight Win­dows, New York, NY, 1995).

Ostrom is ghostwriter/editor of seven popular science books. Additionally, she was an editor of Total Breast Health: The Power Food Solution For Health And Wellness by Robin Keuneke, which was chosen as a Publishers Weekly “Best Book of 1998” in the category of Breast Health (Kensing­ton Publishing Corp., April 1998).