Researchers at the University of Pennsylvania have shown that combining very successful technologies against cancer and COVID-19 vaccines can effectively treat the underlying cause of heart disease.
So far, success has only been achieved in mice, but this stage offers hope for millions of people whose heart muscle is damaged by scar tissue.
There is no effective treatment for this fibrosis, which leads to heart disease, which is the leading cause of death in the United States, said Dr. Jonathan Epstein, a Penn professor who helped run a new study on cardiovascular research, Science on Thursday. published in the journal. .
In his new study, Epstein altered fibrosis by remodeling cells as in the successful treatment of blood cancer called CAR-T. However, in this case, the treatment took place inside the body, not in a laboratory vessel.
The team carried out the treatment using mRNA technology, as evidenced by the hundreds of millions of people who received mRNA-based COVID vaccines last year.
“If it works (in humans), it can have a really big impact,” Epstein said. “Almost every type of heart disease comes with fibrosis.”
About 50% of heart failure is caused directly by this scar tissue, which prevents the heart from relaxing and pumping efficiently. Fibrosis is also involved in the underlying causes of lung and kidney disease.
In a decade-long CAR-T approach to the fight against leukemia, developed in Penn by research co-author Carl June, a patient’s immune cells are removed from the body and genetically modified to identify tumor cells. They are then repositioned to destroy the cancer.
CAR-T, which represents chimeric antigen receptor T cells, has become very expensive because it is tailored to each patient. By working inside the body,the new approach allows treatment with the same general approach for all.
“It can be expanded now. It makes me even more excited,” Epstein said.
He said that unlike cancer therapy, where every last cancer cell must be killed to prevent recurrence in fibrosis, almost any significant reduction improves one’s quality of life.
While there is still a long way to go to help people, this method shows the potential of mRNA technology, which is beyond COVID vaccines.
“It’s great,” said Dr. Crystal McCall, a cancer researcher at Stanford University who uses CAR-T to treat cancer and hasn’t been involved in the study. “I think we all knew that the COVID vaccine was so successful and well tolerated by so many people … those of us who are scientists immediately think, ‘Wow, what else can I do with this?’ we started. “
In the COVID vaccine, mRNA stimulates cells to produce a protein that is commonly foundon the surface of the coronavirus. Thus, when the immune system sees a real virus, it recognizes the protein before it causes serious damage and attacks the virus.
In the new application, mRNA trains cells to produce a protein located on the surface of fibrotic cells, so immune cells destroy them.
In previous studies, the developed T cells were delivered in a way that allowed them to survive for a long time, which increased the risk of the immune system attacking other fibrotic cells, including those involved in wound healing. By delivering the protein with mRNA, it can be preserved for only a few days, researchers think they can avoid this problem.
“The window for potential problems is relatively small,” Epstein said.
This short-term endurance is a big advantage, he and others said.
Dr Stanley Riddell, a professor and immunologist at the Fred Hutchinson Cancer Research Center in Seattle, said: “The idea that this can be done in a matter of days is very exciting. “It’s a very good application of modern synthetic biology.”
However, unexpected problems can occur, and the Penn team goes a long way in safely treating people with fibrotic heart disease, Epstein said.
They then plan to test their approach on larger mammals in about two years before moving on to humans. They still need to develop the most optimal dose and how many times the treatment needs to be carried out to be most effective, he said.
The research team set up a company to help develop the technology.
One advantage of Epstein is that imaging technology can now “see” fibrous tissue, allowing physicians to assess a patient’s disease and response to therapy. “There are already tools to promote that,” he said.
Like many great scientific achievements, the idea of a new approach to treatment began with a random encounter in an elevator.
One of Epstein’s graduate students was loudly surprised about the possibility of using CAR-T to treat heart fibrosis. A few days later, Epstein ran in the elevator in June and asked the same question.
According to Epstein, “they had the power to go back and forth between laboratories” and they were smart enough to study different sciences.
The teams have been working together for several years when Dr. Drew Weissman, a Penn scientist whose research is based on mRNA vaccines, approached them to suggest treatment via mRNA.
“I just went into John’s office and said,‘ We can do this, ’” Weissman said.
Not surprisingly, Weissman has great faith in mRNA technology, which is already being tested in other vaccines – influenza, shingles and respiratory syncytial virus, as well as cancer prevention. New research shows it has a wider potential, he said.
Fibrosis is not only a heart disease, but also a part of many diseases. Duchenne muscle dystrophy, pulmonary fibrosis, scleroderma, and COVID occur as a result of hardening of vital tissue in the lungs, Weissman said, currently using mRNA as a basis for an experimental HIV vaccine. Humans are also experimenting with the use of mRNA in the treatment of autoimmune diseases and in gene therapy.
“His potential is really huge,” Weissman said. “This is the beginning of the RNA world.”
Contact Karen Weintraub at firstname.lastname@example.org.
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