Public Release: 

Gene therapy improved left ventricular and atrial function in heart failure by up to 25 percent

Intracoronary delivery of gene vector was safe and improved heart function in a large animal model

The Mount Sinai Hospital / Mount Sinai School of Medicine

(New York - Sept. 25, 2017) -- Heart function improved by up to 25 percent in a trial using gene therapy to reverse cardiac damage from congestive heart failure in a large animal model, Mount Sinai researchers report. This is the first study using a novel vector for gene therapy to improve heart function in non-ischemic heart failure.

The results of the study will be published online in the Journal of the American College of Cardiology.

In heart failure, a weakened or damaged heart no longer pumps blood effectively. This potentially fatal disease affects almost 6 million Americans, according to the American Heart Association, and is a major cause of morbidity and mortality, especially in elderly patients. Despite this toll, there has been little progress toward any kind of cure. Novel therapeutic approaches, such as gene therapy and cell therapy, hold the promise of complementing or replacing existing therapies for congestive heart failure.

"Mount Sinai has performed pioneering work on gene therapy over the last decade, and this study shows that gene therapy is now a viable option for treating congestive heart failure," said the study's senior author, Roger Hajjar, MD, Director of the Cardiovascular Research Center and the Arthur and Janet C. Ross Professor of Medicine at the Icahn School of Medicine at Mount Sinai. "There is a critical need to explore new therapeutic avenues and approaches."

This study featured two independent experiments. The first established the safety of administering a therapeutic gene delivery vector, BNP116, created from an inactivated virus over three months, into 48 pigs without heart failure through the coronary arteries via catheterization using echocardiography. The second experiment examined the efficacy of the treatment in 13 pigs with severe heart failure induced by mitral regurgitation. Six pigs received the gene and 7 received a saline solution.

The researchers determined that the gene therapy was safe and significantly reversed heart failure by 25 percent in the left ventricle and by 20 percent in the left atrium. Heart failure often results in enlarged hearts, and the team found a 10 percent reduction of heart size in the affected animals. Heart failure in the cohort of pigs treated with saline worsened.

The research team plans to study the same gene therapy in a human trial starting next year. The gene vector has been approved by the Food and Drug Administration for clinical treatment.

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This study was supported by NIH P50 HL112324, R01 HL119046, R01 HL117505, R01HL128099, R01 HL129814, R01HL131404, & R43HL108581 (R. J. H.), HL26057, & HL64018 (E.G. K) and a Transatlantic Leducq Foundation grant. The Gene Therapy Resource Program (GTRP) of the National Heart, Lung, and Blood Institute, National Institutes of Health provided some of the gene vectors used in this study. K.I is supported by a grant from American Heart Association 17SDG33410873.

About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest integrated delivery system encompassing seven hospital campuses, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The System includes approximately 7,100 primary and specialty care physicians; 10 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in four other specialties in the 2017-2018 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked in six out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology and 50th for Ear, Nose, and Throat, while Mount Sinai Beth Israel, Mount Sinai St. Luke's and Mount Sinai West are ranked regionally. For more information, visit http://www.mountsinai.org/, or find Mount Sinai on Facebook, Twitter and YouTube.

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