(Ivanhoe Newswire) — Researchers have discovered a new drug target that they say may treat and/or prevent heart failure.
The team of scientists from Mount Sinai School of Medicine studied failing human and pig hearts. They discovered a protein known as SUMO1, which regulates the activity of key transporter genes, was decreased in failing hearts. Heart function was improved when the researchers injected SUMO1 into the hearts via gene therapy.
The investigators were evaluating the transporter gene SERCA2a in patients as part of a clinical trial. When delivered through an inactive virus that acts as a medical transporter into cardiac cells, SERCA2a demonstrated improvement or stabilization with few side effects. However, they found over time, the new SERCA2a became dysfunctional, suggesting that something else upstream from SERCA2a was causing the dysfunction in the heart.
The scientists identified SUMO1 as the regulator of SERCA2a, showing that it enhanced its function and improved its stability and enzyme activity. When SUMO1 decreased, SERCA2a became dysfunctional, showing that SUMO1 plays a protective role. When SUMO1 was injected as a gene therapy, it protected SERCA2a from the oxidative stresses and dysfunction that are present 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,” Roger J. Hajjar, M.D., Director of Mount Sinai’s Wiener Family Cardiovascular Research Laboratories, and the Arthur and Janet C. Ross Professor of Medicine, Mount Sinai School of Medicine, was quoted as saying. “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.”
According to the U.S. 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 who have heart failure die within one year of diagnosis.
SOURCE: Nature, September, 2011