Covid-19 was not a pleasant experience and led to great suffering and many casualties all over the world. However, it now seems that some good is coming from the difficult times since we have gained incredible new knowledge regarding the technology used to create the vaccines, albeit under tremendous time pressure.
The versatile genetic tracking technology, used to create Covid vaccines such as the Pfizer and Moderna vaccines, has now been adapted to help regenerate heart muscle cells that were damaged during cardiac arrests.
Thousands of people in South Africa are hospitalised each year as a result of a heart attack, often caused by blocked arteries (coronary artery disease or atherosclerosis) and a lack of blood supply to the heart.
According to the World Health Organisation (WHO) cardiovascular disease accounts for 17.9 million deaths a year globally – a third of the total number of deaths. Of these, 85 percent are heart attacks and strokes. In South Africa, 225 people die every day from heart disease.
Despite advances in the treatment of people suffering from heart attacks over the past 30 years, up to 45 percent of people with heart failure die within a year of being discharged from hospital, and the majority within five years. We may not realise it, but currently heart failure has a worse prognosis than many forms of cancer.
The problem until now has been that we are born with a set number of cells in our heart from birth to death. The heart cannot heal itself after a heart attack and heart-attack patients usually have to live with the resultant damage and debilitating scars that often lead to further complications and a dependence on certain medicines.
However, scientists under the leadership of Professor Mauro Giacca, from the British Heart Foundation Centre for Research Excellence at the highly rated King’s College London, have endeavoured to find a way to stimulate surviving cells and renew the damaged muscle cells in the heart. They have, therefore, carefully tracked genetic codes called mRNAs (that was also used in Covid-19 vaccines), which produce proteins to generate healthy heart cells.
These scientists use the exact same mRNA (Messenger Ribonucleic Acid) technology as the Pfizer and Moderna Covid-19 vaccines to inject micro RNAs to the heart, thus stimulating the surviving heart cells to proliferate and replace the dead cells. Thus instead of forming a scar, the new technique, called genetic tracking, helps healthy heart muscle cells to replace the dead ones with new muscle tissue. Through a complex cascade of processes inside the cell, this therapy can trigger heart cells to grow and regenerate the way they can early in life.
mRNA is a single-stranded molecule of RNA that uses information genes to create a blueprint for making proteins. A ribosome reads the blueprint when synthesizing a protein to generate healthy heart cells. In the case of the Covid-19 vaccines, the mRNA is delivered to the body’s cells by means of tiny fat droplets known as lipid nanoparticles (LNPs). In the case of the ground-breaking research, the mRNA is injected directly into the heart muscle and is used to instruct the heart cells to repair themselves after a heart attack.
The research team of King’s College London has successfully completed several trials to regenerate damaged mice, rats and pig hearts. It is planned to commence tests on humans in the next two years.
At the University Medical Centre Utrecht in the Netherlands, Dr Clara Labonia injected different LNP formulations into the left ventricular wall of the hearts of mice. Twenty-four hours later the location of mRNA translation was examined. The researchers found that the mRNA successfully reached the heart cells and that LNPs are a suitable delivery system for mRNA therapy.
But Professor Giacca is going further than just the regeneration of heart cells. He and his team is also working towards a treatment to prevent heart cells from dying during a heart attack, thus preventing millions of heart attacks from progressing toward heart failure. The team identified three proteins that stop heart muscles from dying. Injecting them immediately after a heart attack helps to save the heart muscles. Cardiac arrests causes acute trauma to the heart muscle and kill a huge number of heart cells.
At Sweden’s Karolinska Institute, Professor Kenneth Chien, the co-founder of the mRNA giant Moderna, is busy with similar research to repair heart function after damage. This would save many people waiting for a heart transplant.
The study, published on May 12 in Nature Cell Biology, described the investigation of an enriched pool of human pluripotent stem cell derived ventricular progenitors (HVPs) to restore heart function. The researchers discovered HVPs can detect damaged heart muscle, migrate to the injury site, and mature into working heart cells.
Professor Chien and his team tested the treatment on pig hearts and illustrated that damage can be reliably repaired without serious side effects. New cardiac tissue was formed, cardiac function was improved, and scar tissue reduced. The research will in the coming years be expanded to human treatment.
Previous experiments to restore heart tissue entailed the use of heart cells grown from stem cells, but serious side effects such as irregular heartbeats and fatal arrhythmia have been encountered.
More recent research included studies to treat or repair heart damage by modifying mRNA to instruct heart cells to repair themselves (University Medical Centre Utrecht); combining mRNA technology and CAR-T (Chimenic antigen receptor T-cell) therapy – a type of immunotherapy in the treatment of blood cancers (University of Pennsylvania); transiently returning adult cardiomyocytes to a foetal-like state by selectively expressing four genes essential for cell renewal (Max Planck Institute for Heart and Lung Research); and vascular endothelial growth factor A (VEGF-A) mRNA that forms new blood vessels (AstraZeneca).
Treatment for heart attacks and heart failure remains very similar to 50 years ago, with the main forms of therapy drugs that were developed in the 1970s, namely beta-blockers and angiotensin-converting enzymes (ACE) inhibitors.
This ground-breaking new RNA research is certainly pushing the boundaries of medical science and could revolutionise cardiovascular medicine and create the world’s first ever cure for victims that suffered heart damage due to a deadly heart attack. It could even prevent millions of heart attacks progressing towards heart failure and thus extend the lives of patients. The regeneration of a damaged heart is not a dream anymore, but can become a reality.
Professor Louis C H Fourie is an Extraordinary Professor of the University of the Western Cape
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