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mRNA technology used in COVID vaccines might one day treat heart disease, study suggests

Though the Penn research involved mice, the scientists said it might one day offer hope of a treatment for millions of people whose heart muscle is damaged by scar tissue. 

Dr. Jonathan Epstein, a Penn professor of cardiovascular research who helped lead the new work, published in the journal Science.
Dr. Jonathan Epstein, a Penn professor of cardiovascular research who helped lead the new work, published in the journal Science.
University of Pennsylvania

Combining technologies that proved hugely successful against cancer and in COVID-19 vaccines, at the University of Pennsylvania researchers have shown in a study involving mice that they can effectively treat a leading cause of heart disease.

That’s, of course, only a first step toward possibly doing the same with humans, and what works with mice doesn’t always prove to work the same with people.

Still, the researchers said the finding might one day offer hope of the first effective treatment for millions of people whose heart muscle is damaged by scar tissue.

There is none now for this fibrosis, which leads to heart disease, the leading cause of death in the United States, said Dr. Jonathan Epstein, a Penn professor of cardiovascular research who helped lead the new work, published in the journal Science.

Epstein reversed fibrosis by re-engineering cells, as has been done with a successful blood cancer treatment called CAR-T. In this case, the treatment took place inside the body rather than in a lab dish.

Epstein’s team delivered the treatment using mRNA technology, which has been proven over the last year with hundreds of millions of people getting mRNA-based COVID vaccines.

“If it works [in people], it really could have enormous impact,” Epstein said of using the treatment for heart fibrosis. ”Almost every type of heart disease is accompanied by fibrosis.”

About 50% of heart failure is directly caused by this scar tissue, which prevents the heart from relaxing and pumping effectively. Fibrosis also is involved in leading causes of lung and kidney disease.

A PET scan shows scar tissue in a heart after a heart attack. It’s this scar tissue that a new approach developed at the University of Pennsylvania aims to treat. 
A PET scan shows scar tissue in a heart after a heart attack. It’s this scar tissue that a new approach developed at the University of Pennsylvania aims to treat.
Florian Leuschner

In the decade-old CAR-T approach to fighting blood cancers, which was developed at Penn by study co-author Carl June, immune cells from a patient are taken out of the body and genetically altered to identify tumor cells. They’re then reinserted so they can destroy the cancer.

CAR-T — which stands for chimeric antigen receptor T cells — has been hugely expensive because it’s personalized for each patient. By working inside the body, the new approach would allow treatment with a similar approach made generic to work for everyone.

“It is now scalable,” Epstein said.

Unlike cancer therapy, in which every cancer cell has to be killed to prevent a recurrence, with fibrosis, almost any significant reduction will improve quality of life, he said.

Though years away from helping people even if it proves to work with humans, the method shows what the researchers at Penn and other experts think is the potential of mRNA technology well beyond COVID vaccines.

“It’s really cool,” said Dr. Crystal Mackall a Stanford University cancer researcher who uses CAR-T to treat cancer and wasn’t involved in this work. “I think we all knew when the COVID vaccine was so successful and so well tolerated in so many people … Those of us who are scientists immediately began thinking, ‘Wow, what else can I do with this?’ ”

In the COVID vaccine, mRNA spurs cells to make a protein normally found on the surface of the coronavirus. When the immune system sees the actual virus, that makes it possible to recognize the protein and attack the virus.

In the new application, the mRNA trains the cells to produce a protein found on the surface of fibrotic cells so that immune cells, it’s hoped, will destroy them.

In previous studies, engineered T cells were delivered in a way that allowed them to persist over a long time, which risked that the immune system would attack other fibrotic cells, including those involved in wound healing. By delivering the protein with mRNA, which sticks around only a few days, the researchers think they can avoid this problem.

This short-term duration is a major advantage, Epstein and others said.

“The idea that you could do this over a period of days is actually pretty exciting,” said Dr. Stanley Riddell, an immunology expert at the Fred Hutchinson Cancer Research Center in Seattle. “It’s a very nice application of cutting-edge synthetic biology.”

Still, problems could crop up, and the Penn team is a long way from safely treating people with fibrotic heart disease, Epstein said.

Next, they plan to test their approach in larger mammals before moving on to people, which they hope will be in about two years.

The research team has started a company to advance the technology.

Different teams at Penn had been collaborating for years when Dr. Drew Weissman, whose research underlies mRNA vaccines, suggested delivering the treatment via mRNA.

Fibrosis is also involved in Duchenne muscular dystrophy, pulmonary fibrosis, scleroderma and COVID lung. All are caused by a hardening of vital tissues, said Weissman, who’s using mRNA as the basis for an experimental HIV vaccine. Scientists also are experimenting with mRNA to treat autoimmune disease and deliver gene therapies.

“The potential for it really is enormous,” Weissman said.

Read more at USA Today.