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$500m Alzheimer’s drug scandal: NY scientist behind NIH-funded therapy busted for allegedly manipulating data in 20 research papers – now there are calls for trials to be cut off

  • Scientist Hoau-Yan Wang is accused of doctoring images in research papers
  • Biochemist Kevin Gardner told Science, Wang’s behavior was ’embarrassing’
  • READ MORE: Multiple sclerosis medication may potentially treat Alzheimer’s

Neuroscientist Hoau-Yan Wang is accused of egregious misconduct concerning 20 research papers

Neuroscientist Hoau-Yan Wang is accused of egregious misconduct concerning 20 research papers

Scientists are calling for stage 3 clinical trials of an Alzheimer’s drug to be scrapped after a report highlighted serious doubts about the legitimacy of research that helped the medicine reach that stage.

A long-awaited report by the City University of New York (CUNY) accused one of its faculty members, neuroscientist Hoau-Yan Wang, of egregious misconduct concerning 20 research papers — defined as workplace behavior so outrageous, dangerous, or illegal that an employer cannot reasonably expect to correct it through progressive discipline.

According to the 50-page document obtained by Science, Mr Wang could not provide original data to disprove allegations he had manipulated images in his research papers, many of which provided critical support for the Alzheimer’s drug simufilam’s jump from the lab into clinical studies.

CUNY biochemist Kevin Gardner told Science the report’s findings were ’embarrassing beyond words,’ while Vanderbilt University neuroscientist Matthew Schrag said the ongoing trial should ‘certainly be shut down.’

The allegations were prompted by initial doubts over the doctored images raised by two scientists in August 2021.

Simufilam is a drug in tablet form that claims to prevent the buildup of amyloid proteins in the brain that are a hallmark of Alzheimer's disease

Simufilam is a drug in tablet form that claims to prevent the buildup of amyloid proteins in the brain that are a hallmark of Alzheimer’s disease

The CUNY investigative committee found numerous signs that images in Wang's research were duplicated, cut and pasted, and altered, 'thereby presenting falsified or fabricated biochemical data'

The CUNY investigative committee found numerous signs that images in Wang’s research were duplicated, cut and pasted, and altered, ‘thereby presenting falsified or fabricated biochemical data’

Mr Wang is a long-standing collaborator with biotech company Cassava Sciences, whose work on the experimental Alzheimer’s drug simufilam has been heavily criticized.

Simufilam is a drug in tablet form that claims to prevent the buildup of amyloid proteins in the brain that are a hallmark sign of Alzheimer’s disease. 

Along with Wang, Cassava’s senior vice president for neuroscience Lindsay Burns is also being deemed at fault. Burns is a co-author alongside Wang on some of the papers in question.

The CUNY investigative committee found numerous signs images in Wang’s research papers were used multiple times, cut and pasted, and altered, ‘thereby presenting falsified or fabricated biochemical data.’

One of the papers in question was a 2012 paper published in The Journal of Neuroscience, with both Burns and Wang listed as co-authors, which implied simufilam could reduce the pathological effects of beta amyloid, a protein commonly thought to drive Alzheimer’s disease.

However, the investigative committee could not confirm its total of 31 allegations against Wang, with the majority pertaining to

 because he failed to produce the original raw data. 

The neuroscientist could not provide ‘even a single datum or notebook in response to any allegation,’ the report said. 

Wang’s attorney, Jennifer Beidel Scramlin, told Science neither she nor her client can comment on the report until they speak with CUNY, and that the university has not responded to their inquiries.

CUNY’S report, however, said Wang told the university a ‘significant number of boxes containing research records were thrown away in response to a request from CCNY [City College of New York, part of CUNY] to clean the lab during the Covid-19 pandemic.’

The investigators could not find any evidence of this request.

The internal inquiry began in fall 2021, after previous allegations were forwarded to CUNY by the Office of Research Integrity (ORI), the government body that oversees work funded by the National Institutes of Health (NIH).

The NIH gave millions of dollars to Wang and Burns’ work, including roughly $1.2 million to Wang since December 2020.

According to emails seen by Science, the investigation was not completed until May this year.

Four researchers from CUNY made up the investigative panel, which ran into delays because university officials blocked requests for the image files taken from Wang’s computers.

This resistance went on for six months and was only rectified after the investigators spoke to Vincent Boudreau, the president of CUNY.

Burns and Wang are listed as the joint inventors on multiple patents relating to simufilan, and the pair gave intellectual property rights to Cassava Sciences, known as Pain Therapeutics, in 2019.

Doubts about simufilam first arose in August 2021 when an attorney filed a petition to halt its clinical trials with the Food and Drug Administrators (FDA) on behalf of two neuroscientists — Geoffrey Pitt of Weill Cornell Medicine and David Bredt, a former pharmaceutical executive.

They wanted the trials stopped because they also doubted the accuracy of Wang’s claims in previous research papers. 

The petition covered many of the same papers referenced in the CUNY report, proposing the alleged image manipulation compromised claims the drug may slow down or even backpedal Alzheimer’s symptoms. 

Cassava CEO Remi Barbier, Burns’ husband, questioned if their motives were financial because Pitt and Bredt were short sellers, meaning they could profit if a company’s stock fell.

Barbier also rejected their claims that the pre-trial data had been manipulated, and Cassava Sciences filed a defamation lawsuit against the pair as well as other critics.

In the meantime, investors in Cassava filed their own lawsuit alleging executives at the COMPANY, including Burns and Barbier, deceived them as part of a ‘fraudulent scheme’ to do with how likely simufilam was to succeed.

Cassava carried out small phase 2 trials of the drug in 2019, which it said yielded promising results. It then set up phase 3 trials required to get FDA approval, treating mild-to-moderate Alzheimer’s.

The company has already enrolled more than 800 volunteers and said it will have almost 1,100 by December.

After Pitt and Bredt’s petition, the FDA declined to stop the trials.

Mr Schrag told Science he first gave information to the NIH on Wang’s studies during the summer of 2021. 

He said CUNY’s report is ‘detailed, thorough, and credible.

‘But a two-year delay is somewhat astonishing. … The phase 3 simufilam clinical trials should never have started. And they should certainly be shut down on the basis of this report.’

CUNY has taken no public steps in relation to Wang in the nearly five months since the report was finished.

Senior adviser to the CCNY president Dee Dee Mozeleski told Science Boudreau could not comment on the matter at this time but said ‘action on the report is imminent.’

Cassava Sciences also declined to comment on the report to Science because the university had not sent it to the company. 

It said CUNY did not speak to any Cassava employees as part of the trial and ‘refused all requests for information and offers of assistance from Cassava.’

The biotech firm added it ‘looks forward to continuing the development of simufilam as a potential treatment for patients with Alzheimer’s disease.’

CUNY biochemist Kevin Gardner, who assisted with an initial evaluation of Wang’s work but was not part of the final review, told Science what the panel found was ’embarrassing beyond words.’

He said Dr Wang’s record of research was ‘abhorrent’, and added that the fact his work supported clinical trials is ‘doubly sickening.’

What is Alzheimer’s?

Alzheimer’s disease is a progressive, degenerative disease of the brain, in which build-up of abnormal proteins causes nerve cells to die.

This disrupts the transmitters that carry messages, and causes the brain to shrink. 

More than 5 million people suffer from the disease in the US, where it is the 6th leading cause of death, and more than 1 million Britons have it.

WHAT HAPPENS?

As brain cells die, the functions they provide are lost. 

That includes memory, orientation and the ability to think and reason. 

The progress of the disease is slow and gradual. 

On average, patients live five to seven years after diagnosis, but some may live for ten to 15 years.

EARLY SYMPTOMS:

  • Loss of short-term memory
  • Disorientation
  • Behavioral changes
  • Mood swings
  • Difficulties dealing with money or making a phone call 

LATER SYMPTOMS:

  • Severe memory loss, forgetting close family members, familiar objects or places
  • Becoming anxious and frustrated over inability to make sense of the world, leading to aggressive behavior 
  • Eventually lose ability to walk
  • May have problems eating 
  • The majority will eventually need 24-hour care   

 Source: Alzheimer’s Association

 

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