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A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.

Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.

In a whistleblower report to the NIH about the drug, Dr. Schrag claims that several prominent investigators altered images and reused them over years to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.

“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.

In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.

Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
 

High stakes

Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.

“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.

However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”

Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.

Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.

This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.

However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
 

A matter of trust

Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”

Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”

The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.

Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.

“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.

Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center. 

A version of this article first appeared on Medscape.com.

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A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.

Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.

In a whistleblower report to the NIH about the drug, Dr. Schrag claims that several prominent investigators altered images and reused them over years to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.

“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.

In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.

Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
 

High stakes

Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.

“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.

However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”

Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.

Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.

This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.

However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
 

A matter of trust

Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”

Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”

The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.

Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.

“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.

Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center. 

A version of this article first appeared on Medscape.com.

 

A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.

Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.

In a whistleblower report to the NIH about the drug, Dr. Schrag claims that several prominent investigators altered images and reused them over years to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.

“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.

In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.

Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
 

High stakes

Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.

“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.

However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”

Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.

Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.

This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.

However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
 

A matter of trust

Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”

Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”

The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.

Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.

“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.

Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center. 

A version of this article first appeared on Medscape.com.

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