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UK Scientists Say mRNA Gene Therapy Can Regenerate Human Hearts

Neil lives in Canada and writes about society and politics.
Published: April 19, 2022
UK researchers say they have found a way to use mRNA technology to stimulate human heart muscle tissue to reproduce.
A surgeon wears a binocular loupe during an open-heart surgery in a cardiac surgery unit at the CHU Angers teaching hospital in Angers, Western France, on October 24, 2013. Scientists from King’s College London say they’ve developed a method to utilize messenger RNA gene therapy to create proteins that cause human hearts to regenerate. (Image: JEAN-SEBASTIEN EVRARD/AFP via Getty Images)

Scientists in the United Kingdom claim to have discovered a way to utilize the messenger RNA (mRNA) gene therapy technology to repair the damage inflicted to the human heart during cardiac arrest

In an April 15 article published in The Times, researchers from King’s College London announced the discovery, explaining that the problem heart attack patients face is that human beings are born with a fixed number of heart muscle cells, and they do not reproduce.

When heart muscle is damaged, tissue does not regenerate because the cells possess the unique property of being incapable of dividing. 

While messenger RNA is the same technology utilized in the novel, and often spuriously prone to severe side effect, Coronavirus Disease 2019 (COVID-19) vaccines sold by Pfizer-BioNTech and Moderna, mRNA itself is simply a genetic mechanic utilized in human cells, often in the creation of proteins. 

In the case of the vaccines, a man-made genetic instruction is encapsulated in a man-made lipid nanoparticle, which is to say, a synthetic fat, and introduced to human cells.

The specific genetic instruction is designed to have cells grow the spike protein of SARS-CoV-2, the virus that causes COVID-19, on their surface for the purpose of attempting to elicit an immune response in place of exposure to the actual antigen.

In the case of KCL’s discovery, Professor Mauro Giacca stated that they think mRNA is able to be deployed to repair damage from heart attacks based on the discovery of a trio of undisclosed proteins that can encourage heart cells to repair themselves.

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Giacca called the idea “completely new territory,” and explained the expected use of the therapy is for delivery during an ambulance ride or immediately after hospital arrival post-heart attack. 

One life, one heart

Why doesn’t the heart regenerate?

In a 2015 article, Science Daily cited a study published in the journal eLife by University of Erlangen-Nuremberg (UEN) researchers that stated that in humans and other mammals, cardiac muscle cells lose their ability to reproduce shortly after birth.

The article quotes the authors of the research to state that the reason cardiac cells do not repair and cannot reproduce is because shortly after birth, the centrosome loses proteins and the two centrioles composing it separate.

Researchers currently understand that cells without a wholly intact centrosome cannot reproduce.

According to a terse explanation on the NIH’s National Human Genome Research Institute’s website, the centrosome is a crucial component organelle of human cells.

When cells are about to divide, the centrosome is duplicated and moves to the opposite ends of the cells. As this process occurs, the cell produces microtubules made from proteins, which the centrosomes organize. The microtubules then serve the function of separating replicated chromosomes into daughter cells.

The Institute also explains that centrioles themselves are physical objects made of microtubules, which exist inside centrosomes and serve an inexorable role in chromosome mitosis and cytokinesis.

In the UEN paper, researchers were shocked to discover that unlike humans and other mammals, zebrafish and newts were able to fully regenerate their hearts even after having as much as 20 percent removed.

The highly technical paper elucidates that centrosomes themselves are made of proteins and their component centrioles exist within a cloud of multiple proteins, finding that centrioles split apart in a process arising when centrosome proteins undergo redistribution.

Thus, it stands to reason that there is truth to the idea that certain protein manipulations may be able to cause the centrioles to reconnect, allowing cardiac muscle cells to reproduce and therefore regenerate.

While the KCL team stated in their article with The Times that the technology has successfully been used to regenerate pig hearts, clinical trials on humans aren’t expected to commence for another two years.

Risks and rewards

The methodology of employing protein stimulation via gene therapy may not be without its risks, however.

In a July of 2020 paper published by Giacca himself titled VEGF-B Gene Therapy for the Heart: Proceed With Caution, scientists stated that VEGF-B, an endothelial growth factor protein, induced sympathetic nerve sprouting in mouse and pig hearts when applied by way of an adenovirus vector. 

Notably, adenovirus vector gene therapy is utilized in the AstraZeneca and Johnson & Johnson COVID-19 injections. Utilizing the same principle as the mRNA injections, a sterilized adenovirus is genetically engineered to carry a double stranded DNA payload to human cells to achieve the same purpose.

In the study, the adenoviral vector was utilized to deliver a payload causing the animals to overexpress VEGF-B in an attempt to utilize the nerve sprouting, which affects cardiac innervation, to enhance post-ischemia cardiac recovery. 

However, the study found “an association between a likely disordered nerve sprouting and increased risk of ventricular arrhythmias and sudden cardiac death in pigs, at 6 days after infarction.”