The body’s organs and tissues require a constant supply of oxygen- and nutrient-rich blood to function and stay in good health. Heart failure arises when the heart’s ability to pump blood does not match the body’s needs.
In a healthy heart, the heart muscle contracts and pumps freshly oxygenated blood into the aorta from where it travels to the rest of the body. In a person with heart failure, the heart muscle is weak or damaged and does not fully contract, leaving some blood left to pool inside the organ.
People with heart failure often feel tired and fatigued and may experience shortness of breath as they go about their everyday lives. They can also struggle to breathe when they lie down, and they can put on weight due to swelling in the stomach, ankles, feet, or legs.
The most common causes of heart failure are diseases and conditions that weaken or damage the heart. These include coronary artery disease, heart attacks, high blood pressure, and diabetes. Current treatments can slow or stop the disease from getting worse, but cannot regress it.
Now, researchers in Brazil and the United States claim they have developed and tested a molecule, they named ‘Selective Antagonist of Mitofusin 1-β2PKC Association’ or ‘SAMβA’ for short to help treat heart failures. The experimental drug, when administered in rats with heart ailments was shown to not only stop the heart disease from progressing, but also reduce its severity by improving the ability of heart muscles to contract.
SAMβA works by blocking a specific interaction between two proteins mitofusin 1 (Mfn1) and beta II protein kinase C (β2PKC) whose association impairs mitochondria in heart muscle cells, causing the cells to die. Mitochondria are tiny compartments inside cell bodies that make the chemical energy cells need to function and live. By regulating this specific interaction, the researchers could both halt the progression and make the disease regress to a less severe stage.
Failing hearts overproduce the protein β2PKC. Previous work had shown that blocking the protein improved heart function in people with heart failure, but this also stopped the protein from doing other things that help the heart.
The new drug SAMβA is more selective in that it only blocks one specific interaction, and that is the one that β2PKC has with Mfn1 — the one that affects the function of mitochondria. It does not affect β2PKC’s other interactions. Scientists call the process through which β2PKC alters Mfn1 phosphorylation, and it is one of the ‘most common’ mechanisms in cells for altering the function of proteins.
Tests using human heart cells showed that, like the drugs already in use for the treatment of heart failure, SAMβA could curb the progression of the disease. However, in addition, it could also enhance the ability of cells to contract which is essential for effective pumping of blood.
The researchers cautioned that before clinical treatments can start, the molecule will have to undergo further independent tests, and its compatibility with existing heart failure drugs will also need to be examined.