A group of researchers based in Brazil and the United States have developed a molecule that halts the progression of heart failure and improves the heart’s capacity to pump blood. Rats with heart failure are treat for six weeks with the molecule SAMβA. The disease not only stabilized, as it usually does in response to conventional drug therapy; but actually regressed, thanks to an improvement in the contractile capacity of the cardiac muscle.

Medications currently used

Heart failure may result from myocardial infarction, commonly known as a heart attack; when a blocked coronary artery prevents blood from reaching a section of the heart. The rest of the cardiac tissue is overloaded; and the heart’s capacity to pump blood throughout the body gradually declines over time.

The researchers have applied for a patent on SAMβA and its use in the United States. The molecule may come to supplement or even replace the medications currently used to treat heart failure; most of which are develop back in the 1980s. An article describing SAMβA is publish in Nature Communications.

Principal investigator

The name SAMβA stands for “selective antagonist of mitofusin 1-β2PKC association,” referring to the molecule’s capacity to inhibit the interaction between protein kinase C beta 2 (β2PKC); a common protein in heart cells, and mitofusin 1 (Mfn1), a key element of mitochondria, which are the organelles that produce energy for cells.

In this interaction, β2PKC inhibits Mfn1, preventing the mitochondria from producing energy and hence weakening the heart’s blood-pumping action. Because “This interaction was one of our main findings in this study. Its critical role in the progression of heart failure was previously unknown;” said Julio Cesar Batista Ferreira, a professor at the University of São Paulo’s Biomedical Science Institute (ICB-USP) in Brazil and principal investigator for the study.

Mitochondrial dysfunction

Ferreira began research in the field in 2009 when he was a postdoctoral fellow at the same university’s School of Physical Education and Sports (EEFE-USP) with a scholarship from FAPESP – São Paulo Research Foundation. Once the patent has been granted, Ferreira add; the molecule can be tested in connection with hypertension and other cardiovascular diseases.
“We suspect the interaction between these two proteins may be a factor in other degenerative diseases involving mitochondrial dysfunction;” Ferreira told Office. Because  Previous research by Ferreira’s group at ICB-USP showed that the inhibition of β2PKC, which is overproduced in the cells of failing hearts; improved cardiac function in these patients. However, the intervention prevented the protein from acting in other ways that benefit the heart.
The novelty of SAMβA is its selectivity: it inhibits only β2PKC’s interaction with Mfn1 in mitochondria and does not affect the protein’s other actions. Ferreira offers an analogy to explain this selectivity; Therefore comparing a heart cell to a company office with several rooms. β2PKC is an office clerk who moves along the corridors and goes into the different rooms; interacting with the managers of the respective sectors to perform his/her duties.
When he/she enters one particular room (the mitochondrion); however; the office clerk (β2PKC) prevents a particular manager (Mfn1) from doing his/her job. With the first molecule developed by the group; it was as if the doors of all the rooms are close. The office clerk no longer hampered the mitochondrial manager and did not enter any other rooms; the company (heart cell) did not function harmoniously.