Nav: Home

Researchers create SAMβA, a new molecule to treat heart failure

March 12, 2019

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 were treated for six weeks with the molecule, called "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.

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 were developed back in the 1980s.

An article describing SAMβA has been published in Nature Communications. 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.

"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. 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 added, 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.

Clerk and managers

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, 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 were closed. The office clerk no longer hampered the mitochondrial manager and did not enter any other rooms; the company (heart cell) did not function harmoniously.

However, all SAMβA does is prevent β2PKC from interacting with Mfn1 in mitochondria. "It's as if we only closed the door to the room the clerk isn't allowed to enter while leaving him free to go into all the others, so the company can continue functioning properly," Ferreira said.

Infarcted rats

To arrive at SAMβA, the researchers performed tests with recombinant proteins, cells, animals, and samples of cardiac tissue from patients with heart failure.

Ferreira's group first conducted different in vitro experiments to test the interaction between β2PKC and Mfn1. They found six molecules that inhibited the interaction, but only SAMβA did so selectively without influencing other interactions.

Next, SAMβA was tested in human heart cells. In addition to halting the progression of the disease, which is already achieved by the drugs currently in use, the molecule boosted the cells' capacity to contract - an essential part of the job done by the heart in pumping blood throughout the body.

SAMβA also reduced the amount of hydrogen peroxide in heart cell mitochondria. The presence of this peroxide characterizes oxidative stress, which is a trigger of cardiac cell degeneration.

Finally, the researchers induced myocardial infarction in rats. One month later, the rats developed heart failure, and an osmotic pump was implanted under the skin of each rat to release small amounts of SAMβA or an innocuous substance (in the case of the control group) for six weeks.

Unlike the control rats, those that were treated with SAMβA stopped exhibiting heart failure, and their cardiac function improved.

"The drugs in current use halt progression of the disease but never make it regress. We showed that by regulating this specific interaction, we could both halt progression and make the disease regress to a less severe stage," Ferreira said.

The next step is to make SAMβA available to other research groups for testing against other diseases in different experimental models. It will also be necessary to test the molecule's interaction with the drugs now used to treat heart failure.

"Validation and reproduction of our findings by other groups are critical to the process of developing SAMβA for use in treating heart failure. We will be seeking partners in the private and public sectors for this purpose," Ferreira said.

Cardiovascular diseases kill 17.9 million people annually, causing 31% of all global deaths, according to the World Health Organization (WHO). Acute myocardial infarction with subsequent heart failure is a major cause of morbidity and mortality worldwide.
-end-
About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at http://www.fapesp.br/en and visit FAPESP news agency at http://www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

Fundação de Amparo à Pesquisa do Estado de São Paulo

Related Heart Failure Articles:

Autoimmunity-associated heart dilation tied to heart-failure risk in type 1 diabetes
In people with type 1 diabetes without known cardiovascular disease, the presence of autoantibodies against heart muscle proteins was associated with cardiac magnetic resonance (CMR) imaging evidence of increased volume of the left ventricle (the heart's main pumping chamber), increased muscle mass, and reduced pumping function (ejection fraction), features that are associated with higher risk of failure in the general population
Transcendental Meditation prevents abnormal enlargement of the heart, reduces chronic heart failure
A randomized controlled study recently published in the Hypertension issue of Ethnicity & Disease found the Transcendental Meditation (TM) technique helps prevent abnormal enlargement of the heart compared to health education (HE) controls.
Beta blocker use identified as hospitalization risk factor in 'stiff heart' heart failure
A new study links the use of beta-blockers to heart failure hospitalizations among those with the common 'stiff heart' heart failure subtype.
Type 2 diabetes may affect heart structure and increase complications and death among heart failure patients of Asian ethnicity
The combination of heart failure and Type 2 diabetes can lead to structural changes in the heart, poorer quality of life and increased risk of death, according to a multi-country study in Asia.
Preventive drug therapy may increase right-sided heart failure risk in patients who receive heart devices
Patients treated preemptively with drugs to reduce the risk of right-sided heart failure after heart device implantation may experience the opposite effect and develop heart failure and post-operative bleeding more often than patients not receiving the drugs.
How the enzyme lipoxygenase drives heart failure after heart attacks
Heart failure after a heart attack is a global epidemic leading to heart failure pathology.
Novel heart pump shows superior outcomes in advanced heart failure
Severely ill patients with advanced heart failure who received a novel heart pump -- the HeartMate 3 left ventricular assist device (LVAD) -- suffered significantly fewer strokes, pump-related blood clots and bleeding episodes after two years, compared with similar patients who received an older, more established pump, according to research presented at the American College of Cardiology's 68th Annual Scientific Session.
NSAID impairs immune response in heart failure, worsens heart and kidney damage
Non-steroidal anti-inflammatory drugs, or NSAIDs, are widely known as pain-killers and can relieve pain and inflammation.
Heart cell defect identified as possible cause of heart failure in pregnancy
A new Tel Aviv University study reveals that one of the possible primary causes of heart failure in pregnant women is a functional heart cell defect.
In heart failure, a stronger heart could spell worse symptoms
Patients with stronger-pumping hearts have as many physical and cognitive impairments as those with weaker hearts, suggesting the need for better treatment.
More Heart Failure News and Heart Failure Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Climate Mindset
In the past few months, human beings have come together to fight a global threat. This hour, TED speakers explore how our response can be the catalyst to fight another global crisis: climate change. Guests include political strategist Tom Rivett-Carnac, diplomat Christiana Figueres, climate justice activist Xiye Bastida, and writer, illustrator, and artist Oliver Jeffers.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.