Patients receiving a high dose of the therapy, called SERCA2a, experienced substantial clinical benefit and significantly reduced cardiovascular hospitalizations, addressing a critical unmet need in this population. The data are published online in the June 27 issue of the American Heart Association journal Circulation.
SERCA2a is delivered via an adeno-associated virus vector—an inactive virus that acts as a medication transporter—into cardiac cells. The therapy stimulates production of an enzyme within these cells that enables the heart to pump more effectively in people with advanced heart failure. After one year, patients who were administered a high dose SERCA2a demonstrated improvement or stabilization. Gene therapy with SERCA2a was also found to be safe in this sick patient population, with no increases in adverse events, disease-related events, laboratory abnormalities, or arrhythmias compared to placebo.
"Few treatment options have shown such improved clinical outcomes in this patient population in the last decade," said Roger J. Hajjar, MD, Research Director of Mount Sinai's Wiener Family Cardiovascular Research Laboratories, and the Arthur and Janet C. Ross Professor of Medicine, and Gene and Cell Medicine, Mount Sinai School of Medicine. "This study establishes a new paradigm for the treatment of heart failure by clinically validating SERCA2a as a novel target. In addition, by showing that adeno-associated vectors are safe to use in patients with advanced heart failure, this study ushers a new era for gene therapy for the treatment of failing hearts."
The CUPID (Calcium Up-regulation by Percutaneous administration of gene therapy In cardiac Disease) trial is a randomized, double-blind, placebo-controlled study, which enrolled 39 patients with advanced heart failure to study the safety and efficacy of SERCA2a. Patients were randomized to receive SERCA2a gene delivery in one of three doses or placebo, and were evaluated over one year. The treatment is delivered directly to the patient's heart during a routine outpatient cardiac catheterization procedure.
Patients in the high-dose SERCA2a group demonstrated improvement and/or stabilization in symptoms, overall heart function, biomarker activity, and ventricular mechanics and function. They also saw a dramatic reduction in cardiovascular hospitalizations, averaging 0.4 days versus 4.5 days in the placebo group.
"Even though heart failure mortality has decreased over the last decade with the help of standard pharmacological and device therapies, patients with advanced heart failure continue to die at high rates. The CUPID trial offers a new therapeutic option for these patients," said Dr. Hajjar.
Led by Dr. Hajjar, the Mount Sinai team discovered the landmark potential of the cardiac-specific target in 1999 and has been pursuing its potential as a treatment delivered via gene therapy in state-of-the-art custom built laboratories at Mount Sinai School of Medicine in New York.
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. In 2010, heart failure will cost the United States $39.2 billion, including the cost of health care services, medications, and lost productivity. 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.
The CUPID Trial is funded by Celladon Corporation. The company was co-founded by Dr. Hajjar who has an equity interest in Celladon Corporation and participates on an Advisory Board.
About The Mount Sinai Medical Center
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 United States. It has more than 3,400 faculty 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. The school received the 2009 Spencer Foreman Award for Outstanding Community Service from the Association of American Medical Colleges.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. U.S. News & World Report consistently ranks The Mount Sinai Hospital among the nation's best hospitals based on reputation, patient safety, and other patient-care factors. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 530,000 outpatient visits took place.
For more information, visit http://www.mountsinai.org/.Find Mount Sinai on:
Mount Sinai Press Office | EurekAlert!
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Materials Sciences
23.03.2018 | Agricultural and Forestry Science
23.03.2018 | Physics and Astronomy