Researchers at Mount Sinai School of Medicine, in New York City, have developed a new gene therapy that they claim is safe and effective in reversing advanced heart failure. The gene therapy, SERCA2a, produced under the brand name Mydicar, is designed to stimulate production of an enzyme that enables the failing heart to pump more effectively.

In a Phase II study, SERCA2a injection through a routine minimally invasive cardiac catheterization was found to be safe and showed clinical benefit in treating a patient population and in decreasing the severity of heart failure, researchers say. They presented their findings earlier this month at the Heart Failure Congress of the European Society of Cardiology, in Berlin.

"SERCA2a appears to be safe and effective in people with advanced heart failure," said trial investigator Dr. Jill Kalman, an associate professor of medicine and cardiology at Mount Sinai and director of the school's cardiomyopathy program. "There is a significant unmet need for treatments in this patient population, and these data indicate that SERCA2a is a promising option for them."

The CUPID (calcium up-regulation by percutaneous administration of gene therapy in cardiac disease) trial is a randomized, placebo-controlled study that enrolled 39 patients with advanced heart failure to study the safety and effectiveness of SERCA2a. Patients were chosen at random to receive SERCA2a gene delivery in one of three doses, or a placebo, and were evaluated over six months. The treatment was delivered directly to the patient's heart during a routine outpatient catheterization procedure.

Patients in the SERCA2a group demonstrated improvement or stabilization in symptoms, heart function, and severity of heart failure. They also saw an increase in time between cardiovascular events and a decrease in frequency of events. SERCA2a was found to be safe, with no increases in adverse events, disease-related events, laboratory abnormalities, or arrhythmias.

SERCA2a was developed by a team led by Dr. Roger J. Hajjar, research director of Mount Sinai's Wiener Family Cardiovascular Research Laboratories. The team discovered the landmark potential of the treatment in 1999 and has been pursuing its potential as a gene therapy target in specially built pre-clinical laboratories at Mount Sinai.

"Mount Sinai Heart is committed to developing ground-breaking therapies and bringing them from bench to bedside," said Dr. Valentin Fuster, director of Mount Sinai Heart, the Zena and Michael A. Wiener Cardiovascular Institute, and the Marie-Josee and Henry R. Kravis Center for Cardiovascular Health at the Mount Sinai Medical Center. "We look forward to further study of this important treatment."

About 5.8 million Americans suffer from heart failure, and 670,000 new cases are diagnosed each year, the U.S. Centers for Disease Control & Prevention says. One in five people who have heart failure die within one year of diagnosis, data show.

In 2010, heart failure will cost the U.S. an estimated $39.2 billion, including the cost of health-care services, medications, and lost productivity. Heart failure is treated most often 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.

The CUPID trial is funded by Celladon Corp., makers of Mydicar. The company was co-founded by Dr. Hajjar, who has an equity interest in Celladon and participates on a company advisory board.

The Mount Sinai Medical Center encompasses both the Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of few medical schools embedded in a hospital in the U.S. It has more than 3,400 faculty members in 32 departments and 15 institutes, and ranks among the top 20 medical schools both in National Institute of Health funding and by U.S. News & World Report.