Veterans to Be Among First to Receive Investigational Cell Therapy for Heart Failure Under $10 Million Department of Defense Grant

Cedars-Sinai Heart Institute Investigators to Collaborate With Investigators From Medical University of South Carolina, Ralph H. Johnson Department of Veterans Affairs to Study Hard-to-Treat Condition

Contact Sally Stewart | Email: sally.stewart@cshs.org

Los Angeles — Sept. 27, 2016 — Building on the results of a Cedars-Sinai Heart Institute study published six months ago, the U.S. Department of Defense has awarded a $10 million grant to fund a cardiac cell therapy trial for patients diagnosed with a common but difficult-to-treat form of heart failure.

The grant also calls for Cedars-Sinai researchers to continue investigating how and why cardiac progenitor cells are effective in treating laboratory rats that have heart failure with preserved ejection fraction. The condition affects more than half of all heart failure patients and was formerly known as diastolic heart failure.

A key study published in March of this year in the Journal of the American College of Cardiology: Basic to Translational Science showed that weeks after receiving infusions of cardiac-derived cells (CDCs), the heart-pumping function returned to normal in laboratory rats that had hypertension and heart failure with preserved ejection fraction. CDCs are cardiac progenitor cells that are already being studied in clinical trials for other types of heart disease and for Duchenne muscular dystrophy.

The March study, funded by the Cedars-Sinai Board of Governors Heart Stem Cell Center, prompted the U.S. Food and Drug Administration to approve the upcoming clinical trial of CDC infusions for heart failure patients. The trial will take place at the Ralph H. Johnson Department of Veterans Affairs Medical Center and the Medical University of South Carolina, both in Charleston, South Carolina. Civilians and veterans alike may participate in the study.

"We don't know all the details of how it works, so there is exciting science to be done," said Eduardo Marbán, MD, PhD, director of the Cedars-Sinai Heart Institute. "But we already have good reason to believe that CDCs may be effective against a condition that currently has no approved treatments. There is an enormous unmet medical need for these patients."

Heart failure with preserved ejection fraction (often abbreviated as HFPEF and pronounced heff-peff) affects 3 million in the U.S. alone. It is a condition in which the heart muscle becomes so stiff that its pumping chambers cannot properly fill with blood. Even though the heart's ability to contract remains normal, its inability to fill with blood can lead over time to fluid congestion, especially in the lungs.

The condition, particularly common in women and in patients who also have diabetes, obesity or hypertension, leads to extreme fatigue and difficulty breathing.

Currently, patients with the condition might be prescribed medications such as diuretics to reduce the buildup of fluid in the lungs.

"Symptoms might improve after taking diuretics, but currently, we do not have anything to treat the underlying condition," Marbán said. "If cardiac-derived cells prove effective, millions of patients and their families will benefit."

Michael R. Zile, MD, is directing the clinical trial in Charleston, in collaboration with Cedars-Sinai investigators and with Capricor Inc., a clinical-stage biotechnology company. Capricor will collaborate on various aspects of clinical trial execution, including manufacturing CAP-1002, the company's product name for CDCs from human donor-quality hearts, for the trial.

Meanwhile, Cedars-Sinai's Los Angeles-based investigators in four different laboratories will try to understand and identify exactly how cardiac-derived cells work to improve heart health. The parts of the project include:

  • Jennifer Van Eyk, PhD, seeking to identify biochemical markers that may help predict patients' responses to stem cell treatments
  • Robin Shaw, MD, PhD, and TingTing Hong, PhD, working to pinpoint protein changes in patients before and after stem cell treatments
  • Joshua Goldhaber, MD, looking into the role calcium plays in the development of heart failure with preserved ejection fraction
  • Marbán, leading research into whether benefits of the stem cell treatment are due to exosomes, microscopic bodies secreted from cells

"Medical science is just beginning to understand the potential of regenerative medicine to treat heart failure," Zile said. "We hope that this trial is a building block toward a more complete understanding of the mysteries of HFPEF and how we can effectively treat affected patients."

The Department of Defense Peer Reviewed Medical Research Program grant # W81XWH-16-1-0592 is titled: "Heart Failure with Preserved Ejection Fraction: Mechanisms and Novel Therapeutics."

General support for Marbán's laboratory is provided by the National Institutes of Health. The CDCs, manufactured by Capricor (NASDAQ: CAPR) as CAP-1002, have been used in other human clinical trials. General support for Zile's laboratory is provided by the National Institutes of Health and the U.S. Department of Veterans Affairs.

The process to grow cardiac-derived stem cells was developed by Marbán when he was on the faculty of Johns Hopkins University and was further developed at Cedars-Sinai. Capricor has licensed the process from Johns Hopkins and from Cedars-Sinai for clinical and commercial development. Capricor has licensed additional intellectual property from Cedars-Sinai and the University of Rome. Cedars-Sinai and Marbán have financial interests in Capricor.

About the Cedars-Sinai Heart Institute

The Cedars-Sinai Heart Institute is internationally recognized for outstanding heart care built on decades of innovation and leading edge research. From cardiac imaging and advanced diagnostics to surgical repair of complex heart problems to the training of the heart specialists of tomorrow and research that is deepening medical knowledge and practice, the Cedars-Sinai Heart Institute is known around the world for excellence and innovations.