mRNA COVID vaccine offers hope for heart diseases -Expert

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The researchers at the University of Pennsylvania have shown they can effectively treat a leading cause of heart disease with combining technologies that proved hugely successful against cancer and in COVID-19 vaccines.

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Dr. Jonathan Epstein, a Penn professor of cardiovascular research who helped lead the new work, published this on Thursday in the journal Science. For now the success has only been achieved in mice, but the milestone 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, the leading cause of death in the United States, Epstein said.

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

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

“If it works (in people), it really could have enormous impact,” Epstein said. “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.

PET scan shows the 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.

In the decade-old CAR-T approach to fighting blood cancers, developed at Penn by study co-author Carl June, immune cells from the patient are taken out of the body and genetically altered to identify tumor cells. Then, they’re 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 every patient. By working inside the body, thenew approach would allow treatment with the same generic approach for everyone.

It is now scalable. That makes it to me really more exciting,” Epstein said.

“Unlike cancer therapy, where every last cancer cell has to be killed to prevent recurrence, in fibrosis, almost any significant reduction will improve someone’s quality of life,” he said.

Though still a long way from helping people, the method shows 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 was not 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 foundon the surface of the coronavirus. That way, when the immune system sees the actual virus, it will recognize the protein and attack the virus before it can do serious damage.

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

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

“The window for potential trouble is relatively small,” Epstein said. This short-term durability is a major advantage, he and others said.

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

 

 

Okwuego/USA Today

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