Building on the results of a recent Cedars-Sinai Heart Institute study published just six months ago, the 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 with heart failure with preserved ejection fraction, a condition that affects more than 50 percent of all heart failure patients and which 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 and Translational Science showed that weeks after receiving infusions of cardiosphere-derived cells (CDCs), the heart-pumping function returned to normal in laboratory rats with 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 Food and Drug Administration to approve the upcoming clinical trial of cardiac-derived cells (CDC) infusions for heart failure patients at the Ralph H. Johnson Department of Veterans Affairs Medical Center, and the Medical University of South Carolina 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 phonetically as "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 over time can lead to fluid congestion, especially in the lungs. The condition, particularly common in women and in patients who also have diabetes, obesity and/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 cardiosphere-derived cells work to improve heart health. The various 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."