Experimental treatment repairs cells after heart attack

  • Researchers have developed an experimental treatment capable of repairing and regenerating heart muscle cells after a heart attack.
  • After one month of treatment, mouse models of heart attack regained cardiac function close to that of usual.
  • The researchers aim to test the technology in other animal models before entering clinical trials.

Heart failure occurs when the heart cannot pump enough blood and oxygen throughout the body. In 2018, 379,800 death certificates, or approximately 13.4% of deaths, in the United States refers to the condition.

Most cases of heart failure occur due to a loss of cardiomyocytes – heart muscle cells – that results from aging and conditions such as heart attacks, high blood pressure and coronary heart disease. The damage caused by these conditions can irreparably damage the heart.

Although heart transplants are the standard treatment option for heart failure, the limited availability of donor hearts and the risk of rejection limit their widespread use.

Meanwhile, efforts to produce lab-grown cardiomyocytes from pluripotent stem cells have also failed to produce long-term results.

Finding ways to repair cardiomyocytes could improve the prognosis of people at risk for heart failure and other cardiovascular diseases.

Recently, researchers have developed a new technology that repairs and regenerates cardiomyocytes in mice following a heart attack.

“Soon after birth, the human heart stops growing by cell replication, and the size of the heart increases by increasing the size of each individual cell,” said Robert Schwartz, professor emeritus in the Department of Biology and Biochemistry at the University. University of Houston at Texas. , and one of the authors of the study. “Thereafter, very few new heart muscle cells are produced during a person’s lifetime.”

“When there is an injury like a heart attack, muscle cells are starved of oxygen and many of them die. As no new cells can be generated, the pumping of the heart can be severely depressed and eventually lead to the dead,” Dr. Schwartz said. Medical News Today.

“What Animatus Biosciences has done is develop a pair of modified synthetic messenger RNAs (mRNAs) that code for proteins capable of restarting the process of cell replication and therefore replacing dead heart cells with new ones. healthy tissue to restore heart function. ,” he explained.

The study was published in the Journal of Cardiovascular Aging.

A transcription factor protein known as serum response factor (SRF) is essential for the creation of new heart cells. The way it interacts with other cofactors gives rise to heart-specific gene activity.

A modified version of the transcription factor YAP1, also present in the heart, known as YAP-5SA, also affects cardiomyocyte proliferation and growth.

In the present study, researchers hypothesized that disruption of interactions between SRF and cofactors could lead to cardiomyocyte dedifferentiation. They wrote that it could complement YAP-5SA and put the cells into a stem cell-like state from which they could grow into new cardiomyocytes.

To test their hypothesis, they administered a mutated version of SRF known as ‘Stemin’ alongside YAP-5SA to a rat cardiomyocyte cell line using modified mRNA (mRNA) technology.

In doing so, they induced cardiomyocyte dedifferentiation among cells and replicated adult cardiomyocytes.

The researchers then administered the experimental treatment to a mouse model of heart attack in another study. Within a day of injection into the left ventricles of infarcted adult mice, they reported a more than 17-fold increase in cardiomyocyte nuclei.

They further noted that the mouse hearts of the mice repaired to almost usual heart pumping within a month and had little scarring.

The researchers concluded that the combination of mRNAs encoding Stemin and YAP-5SA is a promising treatment for human heart disease.

Asked about the limitations of the study, Dinakar Iyer of the Department of Biology and Biochemistry at the University of Houston, one of the study’s authors, said DTM: “The main limitation is that the results of our study are limited to mice only. We plan to repeat the same experiments on pigs and see if we can obtain a similar answer. If the result is similar in pigs, our next approach will be to do a limited study (with FDA approval) in cardiac patients.

Dr Schwartz added: ‘It is possible that the mRNA combination may not work in human patients, but since the genetic pathways activated by our mRNA combination are very similar in all mammals, we are confident that they will also work in humans. .”

Asked what this new technology could mean for future treatment options for cardiovascular disease, Bradley McConnell, Ph.D., FAHA, FCVS, professor of pharmacology at the University of Houston, author of the study, said DTM:

“This new heart repair technology could help reduce the need for left ventricular assist devices (LVADs) – a mechanical device that serves as a transition therapy to transplantation or even a destination therapy to repair the human heart after a heart attack. .”

“Instead, injecting synthetic mRNAs expressing Stemin and YAP-5SA into the damaged heart could replace this battery-powered LVAD pump,” he continued.

Dr Iyer added: “Our Animatus Biosciences-supported study is unique in that we use mRNA (messenger RNA) technology, as in current highly effective mRNA vaccine preparations against COVID.

“In a hospital setting, Stemin and YAP-5SA mRNA could be directly injected into a patient’s infarcted heart. The mRNA carries the instructions to make the two specific proteins, and once its job is done, i.e. the infarcted heart is repaired, the mRNA is broken down by the body,” he said. he concluded.

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