Days by Harvard Medical The school said that it found extensive counterfeit or manufactured data from the laboratory of a…
Days by Harvard Medical The school said that it found extensive counterfeit or manufactured data from the laboratory of a distinguished cardiac scientist. Doctors and researchers call on a medical examination that was partially founded on his work. They say that sick people should not be exposed to risks with an experiment whose underlying science has been questioned.
In the ongoing tax-paid trial, cardiac stem cells are injected into the hearts of people with heart failure, hoping that these cells – alone or in combination with others ̵
1; will improve patients’ cardiac function.
The regenerative effects of these cells were first reported by an influential but controversial researcher, Piero Anversa, whose work has been thrown into question. Harvard revealed that a year-long investigation had identified “fake and / or manufactured data” in 31 papers from his laboratory without specifying which publications were concerned. Last year, Harvard-affiliated Brigham and Women’s Hospital, where Anversa worked until 2015, reached a resolution of $ 10 million with the Justice Department to resolve allegations that fraudulent data had been used by Anversa’s Laboratory in federal grant applications financing. 19659006] On Wednesday, the New England Journal of Medicine drew a paper and flagged two others with an “Expression of Worry” intended “to indicate that the information presented in the articles mentioned above may not be reliable.” The newspaper said it waits for more information about the two papers.
New York Medical College, where Anversa previously worked, released a statement saying “serious concern” has arisen about a 17-year study. It was considered that an investigation has been initiated.
Anversa is not directly involved in the heart failure test, run by a federal federal funded clinical trial network of $ 63 million. But in view of the concern and the uncertainty about the work that helped the foundation of the trial, external researchers demanded a break and careful examination of whether it would go ahead. The experiment causes inherent risks, as it requires an invasive biopsy that can cause serious complications.
A patient died after the heart was perforated during a biopsy.
“I think the trial should be stopped and they should have an external review,” said Darryl Davis, a cardiologist at the University of Ottawa Heart Institute, studying how to regenerate cardiac tissue. “The Anversa data formed part of the motivation for that experiment, and I think we must understand better what these cells can actually do before we expose patients to the risk of an invasive procedure.”
Anversa’s laboratory did the groundwork in this area and provided cells to a previous clinical trial cited as part of the supporting evidence for the current trial. However, the National Heart, Lung and Blood Institute does not consider the trial to rely on Anversa’s work, according to Denis Buxton, Head of the Basic and Early Translational Research Program at the Institute. Buxton said that the trial was based instead on an idea that emerged from Anversa’s original work – that the cells secrete different molecules that help regenerate muscle tissue, even though it said it was not “a well-known effect at the moment”.  “Several preclinical studies have shown improvement in cardiac function, and patients with advanced heart failure do not really have any treatment options and have poor survival,” Buxton said. There is “convincing need for new therapies that can improve the quality of life of these patients. I think the feeling is that this attempt has the potential to provide such an alternative.”
He said that a patient monitoring patient safety in clinical trials would now get tasked with evaluating the information in connection with the 31 missions requested by Harvard and that patients should be informed of the board’s recommendations.
Anversa’s lawyer said his client is in charge of the scientific findings in his paper and that Anversa only learned from the Harvard investigation that a long-term colleague who left his lab in 2013 had incorrectly changed pictures. Anversa says that in many cases these images can be replaced with correct pictures, and the results will still stand, said his lawyer.
“There is nothing wrong with c-kit positive cardiac stem cells and the attempt will answer the questions about their effect in patients,” Anversa said in an email.
Anversa’s work continued to grow with great enthusiasm about stem cells in the early 2000s. Anversa and colleagues found a type of cardiac cells called c-kit cells could give rise to cardiac muscles and opened new opportunities to help heal physicians after heart attacks or to reverse heart failure.
The discovery quickly led to clinical trials. The current trial, called CONCERT-HF, is partly based on a previous clinical trial in which Anversa’s lab created c-kit cells that would be infused into the patients’ hearts. The report of the results of that trial is now overshadowed by questions about the integrity of stem cells that were formed and characterized in Anvers Laboratory in Boston and then sent to Louisville where they were put in patients.
Roberto Bolli, the University of Louisville Cardiologist who led the trial, told the Washington Post that the work as his team had nothing to do with cell production in Boston. He said that he still does not have enough information about the problems in Anversa’s laboratory to know if they affect the cells to the patients.
“This is obviously a big problem and we try to clarify this important issue,” Bolli
National Heart, Lung and Blood Institute said CONCERT did not base on Anversa’s explanation of how c-kit cells work but on one alternative mechanism that got traction like other researchers who were not affiliated with Anversa’s lab found the cells were not turned to the heart muscle, and instead die or melt with other cells. To explain the effects of the cells on cardiac function in animal studies, some researchers say that the c-kit cells do not regenerate, but secrete different substances and exert what is called paracrine effects.
Anversa told the Post that the CONCERT trial is based on his work and said in a telephone conversation: “I’m not sure I really understand why the trial should be stopped.”
In the CONCERT trial, cells are harvested from the heart and bone marrow of the patients. Two types of stem cells are made from these cells and then injected back into the patient’s bodies – with patients randomly assigned to four different groups that either receive c-kit cells, bone marrow-mediated cells, both types or a placebo. Patient death occurred after a biopsy of the person’s heart cells and before the stem cells were implanted.
“I think it’s time to pause and evaluate things like the CONCERT trial,” said Deepak Srivastava, chairman of Gladstone Institute and presidential election of the International Society for Stem Cell Research. “And if there is no reason for that, I believe in most areas that most such trials would be stopped.”
Elizabeth McNally, a cardiologist and head of the Center for Genetic Medicine at the Northwestern University’s Feinberg School of Medicine, said that Years ago, she was excited by the results from Anversa’s lab, but had problems copying them herself. She described a “religious fervor” that included those who thought that c-kit cells regenerated the heart that continued as researchers have attempted to find factors that could be responsible for what she described as “small to nonexistent” effects. 19659029] “It’s a disappointment that it took so many years for this to come out,” said McNally. “It’s a matter of trial should even go on, and I think at the highest level that the people who support the trial really should review it.”
Charles Murry, director of the Institute of Stem Cells and Regenerative Medicine at the University of Washington expressed concern about patient safety in the trial.
“Given that the scientific premise of this trial is no longer valid, there are no potential benefits that warrant the risk,” Murry said. “If I led this attempt, I think I would stop it based on the latest developments.”