messenger RNA technology holds promise for heart disease

This technology, still unknown two years ago, is now the subject of many avenues of scientific research: messenger RNA. Since the arrival of the anti-Covid vaccination, the RNA molecule has indeed been talked about a lot. Two first mRNA vaccines were marketed at the end of 2020, to fight against Covid-19. In the case of anti-Covid vaccination, it is the mRNA coding for the protein that allows the SARS-CoV2 virus to enter our cells, the Spike protein. Our cells then manufacture this protein and “present” it on their surface. The immune system recognizes it as if it were carried by the virus itself and activates the defense mechanisms and the memory response. Following this, the cells which have received the mRNA and express the protein of interest on their surface are rapidly destroyed. Clearly, messenger RNA, a copy of DNA, provides the blueprints for constructing proteins in our cells.

One of the advantages associated with RNA vaccines (Pfizer and Moderna) is their speed of development, because compared to traditional vaccines, the advantage of this approach is the ease of producing an mRNA. Thus, there is no need to cultivate potentially dangerous germs and to purify some of their components, two complex and expensive processes necessary for the production of conventional vaccines. In addition to vaccines, this technology is now at the heart of scientific projects in many therapeutic areas, including heart health. A study unveiled by researchers at the University Medical Center of Utrecht at a congress of the European Society of Cardiology (Frontiers in CardioVascular Biomedicine 2022) reveals that an RNA therapy is currently being tested as a means of repairing the muscle damaged heart after a heart attack (myocardial infarction).

Cancers, autoimmune diseases… other avenues of research

Their therapy is, rather than aiming for an immune response, to ‘command’ heart cells to repair themselves after a heart attack, which occurs when the supply of oxygen-rich blood to the heart muscle is cut off. The preliminary study called “ Modified mRNA delivery to the heart using lipid nanoparticles was conducted to determine if mRNA could be successfully delivered to heart muscle in lipid nanoparticles (tiny droplets of fat). The researchers injected different formulations into the left ventricular wall of the heart of mice during chest surgery under general anesthesia. Twenty-four hours after the administration of this therapy, the researchers examined the heart tissue of these mice to find out the location of the messenger RNA in the heart tissue: has the molecule reached the targeted heart cells?

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The researchers found that mRNA reaches heart cells 24 hours after injection. However, despite injection into the heart, the highest levels of mRNA translation were found in liver and spleen cells. Study author Dr. Clara Labonia said that a “ high expression was expected in the liver, as this organ metabolizes lipid nanoparticles. It was encouraging to see that there was translation of mRNA in heart tissue, which means that lipid nanoparticles could function as delivery systems for mRNA therapy. The next step for the scientific team will be to test more formulations and choose the one that most effectively targets heart muscle cells. ” Next, we will assess whether delivering mRNA to mice whose hearts have suffered a heart attack has a therapeutic effect.. “, conclude the researchers.

It should be noted that according to Inserm, dozens of RNA therapies are being developed for numerous indications. Particularly, “ several clinical trials are underway around the world to evaluate mRNA vaccines intended to protect against influenza, Zika virus or cytomegalovirus. “, says the organization. The use of therapeutic RNAs is also booming in oncology, in combination with more conventional treatments: chemotherapy, hormone therapy, radiotherapy, etc. Finally, in the case of autoimmune diseases, the idea would be to use RNAs to rehabilitate the immune system that attacks healthy cells in the body, stimulating the production of regulatory T cells. “ The approach is being developed in the treatment of multiple sclerosis, but these developments could benefit patients with Crohn’s disease or ulcerative colitis. »concludes Inserm.

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