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A few days after Harvard Medical School reported having found a lot of falsified or fabricated data from a leading cardiology researcher's laboratory, doctors and scientists urged that a partially-founded medical trial be stopped. on his works. They say that sick people should not be subject to the risks of an experiment whose underlying science has been questioned.
As part of the taxpayer-funded ongoing trial, cardiac stem cells are injected into the heart of people with heart failure, in the hope that these cells, alone or associated with d & # 39; Others, will improve the patient's cardiac function.
The regenerative effects of these cells have been reported for the first time by an influential but controversial scientist, Piero Anversa, whose work has been questioned. Harvard revealed that a multi-year investigation had identified "falsified and / or fabricated data" in 31 documents from its laboratory, without specifying which publications were affected. Last year, the Brigham and Women's Hospital affiliated with Harvard, where Antwerpa was working until 2015, reached an agreement with the Department of Justice on $ 10 million so to resolve the allegations that fraudulent data were used by the Antwerpa laboratory in connection with applications for federal grants.
On Wednesday, the New England Journal of Medicine withdrew an article and reported two more with a "concern" to indicate that the data presented in the articles named above may not be reliable. " The newspaper said it expects more information on both newspapers.
The New York Medical College, where Antwerpa previously worked, issued a statement in which it was stated that "serious concerns" had been raised about a 17-year-old study. He said that an investigation had been opened.
Antwerpa does not participate directly in the heart failure trial, which is managed by a national clinical trial network with $ 63 million in federal funding. But given the turbulence and uncertainty surrounding the work that laid the groundwork for the trial, outside researchers asked for a pause and careful consideration of its relevance. The test carries inherent risks because it requires an invasive biopsy that can lead to serious complications.
A patient died after perforating his heart during a biopsy.
"I think the trial should be discontinued and that an external examination should be performed," said Darryl Davis, a cardiologist at the University of Ottawa Heart Institute. who is studying how to regenerate heart tissue. "The data from Antwerpa were part of the rationale for this trial and I think we need to better understand what these cells can actually do before subjecting patients to the risk of undergoing an invasive procedure. "
The laboratory of Antwerpa performed the basic work in this area and provided cells for a previous clinical trial, cited as evidence to support the ongoing trial. However, the National Institute for the Heart, Lungs and Blood does not consider the trial to be based on the work of Antwerpa, according to Denis Buxton, director of the Fundamental and Early Translational Research Program at l & # 39; institute. Buxton said the trial was based on an idea that stemmed from Antwerpa's original work, namely that cells secrete various molecules that help regenerate muscle tissue, although it is not safe to use. 39; act not a "well characterized effect for the moment".
"Many preclinical studies have shown improved cardiac function, and patients with advanced heart failure really have no treatment options and have poor survival," Buxton said. There is "a pressing need for new treatments that can improve the quality of life for these patients, and I think we feel that this trial could potentially provide such an option."
He added that a committee to monitor patient safety in clinical trials would now be responsible for evaluating the information on the 31 retractions requested by Harvard and that patients would be informed of the committee's recommendations.
The Antwerpa lawyer said that his client was keeping to the scientific conclusions of his papers and that he had learned during the Harvard investigation that Antwerpaonly had learned that a longtime colleague who had left his laboratory in 2013 had altered his images. Antwerpa says that in many cases these images can be replaced by correct images and that the results will still be valid, said his lawyer.
"There is nothing wrong with c-kit-positive cardiac stem cells, and the trial will answer questions about their efficacy in patients," Antwerpa said in an email.
The work of Antwerpa gained momentum in the midst of the broad enthusiasm sparked by stem cells in the early 2000s. Antwerpa and her colleagues discovered that one type of cardiac cells called cells c- Kit were able to give birth to the heart muscle, opening up new possibilities to help heal patients after a heart attack or to reverse heart failure.
The discovery quickly led to clinical trials. The current trial, called CONCERT-HF, is in part based on a previous clinical trial in which the Antwerpa lab had created c-kit cells to infuse into the patients' hearts. The report on the results of this trial is now eclipsed by questions about the integrity of stem cell images created and characterized in the lab from Antwerp to Boston, and then shipped to Louisville, where they were placed on patients.
Roberto Bolli, a cardiologist at the University of Louisville who led the trial, told The Washington Post that his team's work had nothing to do with cell manufacturing in Boston. He said he still did not have enough information about the problems encountered in the laboratory of Antwerpa to know if they were affecting the cells provided to the patients.
"It is obviously of major concern and we are trying to clarify this important issue," Bolli said.
The National Institute of Heart, Lungs and Blood said that CONCERT was based not on the explanation of Antwerpa explaining the functioning of the c-kit cells, but on an alternative mechanism that has is proven, other researchers, not affiliated with the laboratory of Antwerpa, have discovered that cells do not turn into heart muscle, and instead die or melt with other cells. To explain the effects of cells on heart function in animal studies, some researchers now claim that kit cells do not regenerate themselves, but secrete various substances, exerting what is called "cells." paracrine effects ".
Antwerpa told the Post that the CONCERT trial is based on her work and said in a phone interview: "I'm not sure if I understand why the trial should be stopped."
In the CONCERT trial, cells are taken from the heart and bone marrow of patients. Two types of stem cells are made from these cells and then reinjected into the patient's body. Patients are randomized into four different groups receiving c-kit cells, bone marrow derived cells, both types or placebo. The patient's death occurred after a biopsy of the person's cardiac cells and prior to the implantation of the stem cells.
"I think it's time to take a break and evaluate things like the CONCERT trial," said Deepak Srivastava, president of the Gladstone Institutes and president-elect of the International Society for Stem Cell Research. . "And if there is no basis for that, I think in most areas, most events of this type would be interrupted."
Elizabeth McNally, a cardiologist and director of the Center for Genetic Medicine at the Feinberg School of Medicine at Northwestern University, said she was excited about the discoveries of the lab in Antwerp, but that she had then had trouble reproducing them herself. She described a "religious fervor" among those who thought that c-kit cells were regenerating the heart, and who went on to look for factors that could be responsible for what was happening. 39, she described as "minimal or nonexistent" effects.
"It's disappointing that it has taken so many years," McNally said. "The question is whether the trial should even continue, and I think at the highest level, the people who support it should really consider that."
Charles Murry, director of the Institute for Stem Cell Research and Regenerative Medicine at the University of Washington, said he was concerned about the safety of patients participating in the trial.
"Given that the scientific premise of this essay is no longer valid, there does not seem to be any potential benefit to justifying the risk," Murry said. "If I led this trial, I think I would stop it based on these recent developments."
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