Researchers at the University of São Paulo (USP) in Brazil and Foresee Pharmaceuticals have tested a synthetic molecule which could increase heart function in patients with heart failure.
Heart failure is a condition in which the heart cannot pump enough blood to meet the body’s needs for blood and oxygen. A number of drugs can slow its progression but currently no treatment exists that can reverse it.
In the translational study conducted at USP, several experiments were conducted to demonstrate the effect of the molecule, named AD-9308, to restore the activity of the enzyme aldehyde dehydrogenase 2 (ALDH2), which is present in mitochondria and plays a key role in heart failure.
“The study lasted more than ten years and included both laboratory experiments and samples from heart failure patients with the aim of understanding a novel mechanism involved in heart failure progression. In parallel with our experiments, the biopharmaceutical company worked on improving the efficacy of a molecule described back in 2014, which has potential to treat cardiac diseases,” said Julio Cesar Batista Ferreira, a Professor at the Institute of Biomedical Sciences (ICB-USP).
The molecule prototype compound first described (Alda-1) increased heart function by 40% in rats with heart failure, an effect was due to activation of ALDH2 in cardiac cells.
Structural modifications were made to the original molecule to develop AD-9308, which activated the enzyme ALDH2 three times more than the original molecule.
Several studies conducted at ICB-USP have shown that heart failure is associated with mitochondrial malfunction.
“Every cell has hundreds or sometimes thousands of mitochondria, which produce enough aldehyde to poison the entire cell when they aren’t running properly. We discovered in this latest study that too much of 4-hydroxynonenal switches off a vital event for the cell: processing of microRNAs. In addition, we showed that AD-9308 improves mitochondrial filtration enough to eliminate this cellular pollutant,” said Ferreira.