Promising New Drug Target Discovered for Treatment and Prevention of Heart Failure

[ScienceRocks]

Promising New Drug Target Discovered for Treatment and Prevention of Heart Failure


ScienceDaily (Aug. 25, 2012) — A promising new drug target for the treatment and prevention of heart failure has been discovered by researchers at Mount Sinai School of Medicine in New York, NY, US.


Promising new drug target discovered for treatment and prevention of heart failure

The study was presented at the ESC Congress 2012 by principal investigator Professor Roger J. Hajjar, MD.

According to the US Centers for Disease Control and Prevention, about 5.8 million Americans suffer from heart failure and 670,000 new cases are diagnosed each year. One in five people with heart failure die within one year of diagnosis. Heart failure is most often treated with aggressive medical and device therapy, but has no cure. The most common symptoms of heart failure are shortness of breath, feeling tired, and swelling in the ankles, feet, legs, and sometimes the abdomen.

In this study presented at the ESC Congress 2012, researchers identified a new drug target that may treat and/or prevent heart failure. The team evaluated failing human and pig hearts and discovered that SUMO1 (small ubiquitin-like modifier), a small protein that regulates the activity of key transporter genes, was decreased in failing hearts. When the researchers injected SUMO1 into these hearts via gene therapy, cardiac function was significantly improved.

"This indicates that SUMO1 may play a critical role in the pathogenesis of heart failure," said Professor Hajjar, who is research director of Mount Sinai's Wiener Family Cardiovascular Research Laboratories.

Led by Professor Hajjar, the team has been evaluating the transporter gene SERCA2a in patients with severe heart failure as part of the CUPID (Calcium Up-regulation by Percutaneous administration of gene therapy In cardiac Disease) trial. When delivered via an adeno-associated virus vector -- an inactive virus that acts as a medication transporter -- into cardiac cells, SERCA2a demonstrated improvement or stabilisation with minimal side effects. But Professor Hajjar said: "We found that while injection with SERCA2a restored cardiac function, over time the new SERCA2a became dysfunctional. This indicated that something else upstream from SERCA2a was causing the dysfunction in the heart."

Dr Changwon Kho, PhD, and Dr Ah Young Lee, PhD, two experts in the study of cardiac proteins at Mount Sinai School of Medicine, identified SUMO1 as the regulator of SERCA2a, showing that it enhanced its function and improved its stability and enzyme activity. When Professor Hajjar and his team studied human and animal models, they found that when SUMO1 was decreased, SERCA2a became dysfunctional in human hearts, showing that SUMO1 plays a protective role. When the team injected SUMO1 as a gene therapy, they found that it protected SERCA2a from oxidative stresses that are prevalent in heart failure.

"Our experiments over the last four years beginning with the discovery of SUMO1 as an interacting protein of SERCA2a have shown that it plays a critical role in the development of heart failure," said Professor Hajjar. "In fact, SUMO1 may be a therapeutic target at the earliest signs of development and may be beneficial in preventing its progression, a much needed advance for the millions suffering from this disease."

Dr Lisa Tilemann extended the experiments performed in mice and rats in a preclinical model of heart failure in porcine models.
Professor Hajjar said: "We have now clearly shown that SUMO1 gene delivery can enhance cardiac function and stabilize the deteriorations of left ventricular volumes in large animals with severe heart failure. We have also shown that delivering SUMO1 and SERCA2a concomitantly can have synergistic benefits on overall function in heart failure."

This is big news as this is a huge killer.

 

[editec]

Heart disease is the number 1 killer in the USA, so yes this might be VERY big news.

 

[waltky]

possum's favorite Mediterranean food is a Greek lamb gyro...

Mediterranean-style diets found to cut heart risks
Feb 25,`13 : Pour on the olive oil, preferably over fish and vegetables: One of the longest and most scientific tests of a Mediterranean diet suggests this style of eating can cut the chance of suffering heart-related problems, especially strokes, in older people at high risk of them.

The study lasted five years and involved about 7,500 people in Spain. Those who ate Mediterranean-style with lots of olive oil or nuts had a 30 percent lower risk of major cardiovascular problems compared to those who were told to follow a low-fat diet but who in reality, didn't cut fat very much. Mediterranean meant lots of fruit, fish, chicken, beans, tomato sauce, salads, and wine and little baked goods and pastries. Mediterranean diets have long been touted as heart-healthy, but that's based on observational studies that can't prove the point. The new research is much stronger because people were assigned diets to follow for a long time and carefully monitored. Doctors even did lab tests to verify that the Mediterranean diet folks were consuming more olive oil or nuts as recommended.

Most of these people were taking medicines for high cholesterol and blood pressure, and researchers did not alter those proven treatments, said one study leader, Dr. Ramon Estruch of Hospital Clinic in Barcelona. But as a first step to prevent heart problems, "we think diet is better than a drug" because it has few if any side effects, Estruch said. "Diet works." Results were published online Monday by the New England Journal of Medicine and were discussed at a nutrition conference in Loma Linda, Calif. People in the study were not given rigid menus or calorie goals because weight loss was not the aim. That could be why they found the "diets" easy to stick with - only about 7 percent dropped out within two years. There were twice as many dropouts in the low-fat group than among those eating Mediterranean-style.

Researchers also provided the nuts and olive oil, so it didn't cost participants anything to use these relatively pricey ingredients. The type of oil may have mattered - they used extra-virgin olive oil, which is minimally processed and richer than regular or light olive oil in the chemicals and nutrients that earlier studies have suggested are beneficial.

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