University of São Paulo tests molecule to mitigate heart failure

Dicer modification by 4-Hydroxynonenal impairs miRNA maturation in heart failure.


Researchers at the University of São Paulo, Brazil, along with Foresee Pharmaceuticals, a company from Taiwan and the US, have tested a synthetic molecule for treating heart failure. The study was funded by FAPESP and recently published in the European Heart Journal. Heart failure is a serious condition where the heart can’t pump enough blood. It’s a leading cause of death globally, and there are no treatments that can fully reverse it. In Brazil, over 2 million people suffer from it, and sometimes a heart transplant is needed if it gets very severe.

Julio C B Ferreira correseponding author of the article and the proffessor at the Institute of Biomedical Sciences. (ISB-USP)said, ” The study lasted more than 10 years and included both laboratory experiments and sample from heart failure patients with the aim of understanding a novel mechanism involved in heart failure progresssion. In parallel with our experiments, the biopharmaceutical company worked on improving the efficacy of the molecule described back in 2014. which has potential to treat cardiac disease.”

A molecule called Alda-1 was found to boost heart function by 40% in rats with heart failure by activating a specific enzyme in their hearts. Researchers at Foresee Pharmaceuticals improved this molecule and created AD-9308, which is three times more effective. Clinical trials have shown that it’s safe for healthy individuals. To test it on heart failure patients, they need permission from the FDA, a U.S. agency that ensures the safety of drugs.

Heart failure is linked to problems with mitochondria, which are like the engine of the heart. Mitochondria convert energy for the heart to work, but in heart failure, they produce a harmful substance called 4-hydroxynonenal. This substance can harm the cell by interfering with microRNAs, which are important for gene regulation. The new molecule, AD-9308, helps fix the mitochondria and get rid of this harmful substance.

Animals without the Dicer enzyme can develop heart failure. In this study, scientists found that chemical changes caused by heart failure can stop Dicer from working. Dicer is important for making microRNAs, which control how cells work. When Dicer doesn’t work, it can lead to health problems like cancer, metabolic syndrome, and heart disease. The researchers also found that the drug AD-9308 can fix this problem and make Dicer work again in human heart tissue.

“In conclusion, AD-9308 stimulates the removal of aldehyde from sick cells, reducing the likelihood that it will ‘switch off’ Dicer and hence protecting the heart cells. This tends to keep the microRNA profile closer to that of a healthy heart. I consider our partnership with Foresee Pharmaceuticals a success. It’s been essential to our multidisciplinary multicenter research and development, producing highly promising results that can now be trialed in patients,” Ferreira said.

This study holds the potential to bring about a significant breakthrough in the treatment of heart failure, offering hope to the millions of individuals who suffer from this condition. As research progresses, further trials and investigations will be conducted to determine the molecule’s efficacy in treating different forms and stages of heart failure, ultimately aiming to improve the quality of life for those affected by this debilitating condition.

Journal reference:

  1. Ligia A Kiyuna, Darlan S Candido et al., 4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification. European Heart Journal. DOI: 10.1093/eurheartj/ehad662.