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Advanced cancer treatment can also cure some types of heart failure in mice, scientists said Wednesday.
The treatment is a type of immunotherapy called CAR-T, which has changed the lives of some patients with blood cancers. CAR-T relies on genetically modified white blood cells – T cells – that seek out and destroy the body's malignant cells.
In the new study, published in the journal Nature, the technology was used to target scar tissue that stiffens the heart and prevents it from completely relaxing between heartbeats in heart failure patients.
"This is a potentially groundbreaking article," said Dr. Richard Lee, a professor of stem cell biology and regeneration at Harvard, who was not involved in the new study.
Medical experts like Dr. Lee agreed that the study was smart and innovative, and at least a proof of principle. But some have asked if it would be possible to use therapy to treat heart patients, at least in the near future.
For cancer, CAR-T treatment costs about $ 450,000 per patient. When stays at the hospital are included, the price can reach 1 million dollars or more.
There are six million patients in this country suffering from heart failure; even though the treatment at this price was offered to just one a few of them, the overall costs would be astronomical.
Some patients taking CAR-T have serious or life-threatening side effects, such as very high fever, extremely low blood pressure, and brain effects such as confusion and seizures.
The deployment of CAR-T against heart failure "is a really smart idea," said Dr. Douglas Mann, professor of medicine at the Washington University of St. Louis. But considering the cost of CAR-T and the side effects, he added, it's not practical today.
In case of heart failure, the walls of the ventricles, the two large pumping chambers, stiffen and can expand, preventing the heart from effectively pumping blood through the body. This may be due to a number of conditions, including a heart attack and high blood pressure.
While many patients respond to drug treatment, those with a type called heart failure with preserved ejection fraction have few treatment options. Half die within five years, a mortality rate comparable to that of certain metastatic cancers.
Heart failure is a particular problem for people with muscular dystrophy, noted Dr. Lee. Heart failure, he said, "is a major component of life-limiting illness."
The heart muscle stiffens because of scarring, also called fibrosis, said Dr. Jonathan Epstein, lead author of the new study and professor of cardiovascular research at the Perelman School of Medicine at the University of Pennsylvania.
Fibrosis occurs in a variety of other diseases: arthritis, chronic kidney disease and liver cirrhosis, for example. It results from the body's response to inflammation. Although fibrosis is responsible for many of the worst symptoms of these diseases, the effect that the treatment of this fibrosis may have is unclear.
The idea behind this study was born with a student of Dr. Epstein, Haig Aghajanian. He wondered: why can not we do a CAR-T treatment to kill the scar tissue of the heart?
He knew how CAR-T works in the treatment of cancer. The immune system's T cells continually scour the body for unwanted cells that attach to it and kill them. T cells do not sometimes recognize cancer cells, but researchers have found a way to address this problem.
They attach a protein to T cells that are designed to attach to cancer. When these modified T cells drift close to a cancer cell, they hang on to it and kill it.
As long as most healthy cells do not have a host site for this T-cell protein, the treatment may work.
"It's exciting," said Dr. Elizabeth McNally, a cardiologist and geneticist at Feinberg School of Medicine at Northwestern University. But, she warned, any therapy that attacks fibroblasts raises several issues.
These are cells that contribute to the formation of all tissues and play an important role in healing wounds. An ideal treatment should not eliminate fibrosis everywhere, but only the scars that hinder normal functioning.
Until now, Dr. Epstein and his colleagues have not found any healing problems or normal functioning in their animals, but the work is experimental and preliminary.
Dr. Aghajanian and Epstein began by placing a home site on scar tissue cells in the heart of mice with heart failure. Then they made CAR-T cells that attach to these sites.
Two weeks after the treatment of mice, Dr. Aghajanian brought slides to Dr. Epstein. The two men were sitting side by side, looking at them under a microscope. The heart tissue of untreated mice was filled with scars. The heart tissue of the treated mice was clear.
"It was one of those" aha "moments," said Dr. Epstein. "We looked at each other and spent five times under the microscope."
The next step was to look for a natural protein found on human fibrosis cells but not on other cells. The group found a fibroblast activation protein, or FAP, by consulting a large database of genetic data.
Scientists learned that mice and other animals also had FAP on scar tissue cells, so they designed CAR-T cells to look for the protein. The treatment was to remove scar tissue in the mouse heart and did not appear to damage other tissues.
Now, the investigators begin to repeat the experiment in the dog.
"I hope we can move quickly to humans," said Dr. Epstein, noting that a German group found a way to scan the heart of patients with heart attacks and detect APF.
This would allow doctors to quickly know if patients are candidates for CAR-T.
As for the cost, he thinks it will go down. "First-generation treatments are often expensive," said Dr. Epstein. But "success and demand stimulate innovation".
Jeffery D. Molkentin, executive co-director of the Cardiology Institute at the Cincinnati Children's Hospital Medical Center, says he is optimistic about overcoming obstacles.
"It could be transformative," he said.
"All this idea of T-cell engineering to fight cancer is only the tip of the iceberg," he added. "What if we could design T cells to attack all the cells in the body that are causing problems?"
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