Inventing the first DNA repair drug and damaged tissue regeneration

According to Isnaafter a two-decade effort, scientists have discovered the secret to a drug that can repair DNA, paving the way for a new class of treatments that could reverse tissue damage from heart attacks, inflammatory diseases and other diseases.

According to New Atlas, researchers at the Cedars-Sinai Institute achieved this success after developing a technique to isolate progenitor cells from the heart. These cells are very similar to stem cells and can form new healthy tissue in a more targeted way. In other words, these cells taken from the heart can help restore the function of that organ.

Eduardo Marbán, a medical scientist then at Johns Hopkins and now at Cedars-Sinai, discovered that heart progenitor cells also have a special mechanism in which they send out bags called exosomes that carry DNA, RNA and protein molecules between cells and can repair and regenerate damaged tissue.

“Exosomes are like envelopes of important information,” said Ahmed Ibrahim, associate professor of cardiology at the Smith Heart Institute and first author of the study. We wanted to dissect these encoded messages and find out which molecules are themselves therapeutic.

The team attempted to uncover what was in those healing bags. So the material sequenced the exosomal RNA and finally arrived at one molecule that stood out from the rest.

Animal studies focusing on this one RNA molecule confirmed the researchers’ hypothesis that it plays a key role in facilitating tissue repair.

Fast forward two decades and scientists finally made this naturally occurring RNA molecule in the lab, giving birth to a synthetic healer known as TY1.

Marban says: By investigating the mechanisms of stem cell therapy, we discovered a way to heal the body without using stem cells. TY1 is the first exomer, a new class of drugs that target tissue damage in unexpected ways.

TY1 has the structure of existing RNA drugs and acts like its natural version. This exomer boosts the activity of the Trex1 gene, which increases the activity of immune cells that gather around damaged DNA and clear away debris, enabling repair and regeneration. This process is critical following a heart attack to minimize cellular scarring left from the event.

Studies have shown that DNA damage plays an important role in heart failure caused by pressure overload, dilated cardiomyopathy, and heart diseases associated with aging, and this damage to myocardial tissue is a big factor in how well a person recovers from a heart attack.

This approach doesn’t just stop at repairing heart tissue damage, because by increasing DNA repair, we can heal the tissue damage that occurs during a heart attack, says Ibrahim. We are very excited because TY1 is also effective in other conditions, including autoimmune diseases that cause the body to mistakenly attack healthy tissue. This is a completely new mechanism for tissue healing and opens up new options for a variety of disorders.

After animal models, TY1 will next be studied in a clinical trial. If the drug works as expected in humans, it could pave the way for a new class of treatments that could help reduce a wide range of cellular damage caused by acute side effects and chronic inflammatory diseases.

This study was published in the journal Science Translational Medicine.

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