Table of Contents
Willerson Helps Lead Stem Cell Clinical Trial
to Treat Heart Failure
Houston project follows encouraging results with patients in Brazil
The University of Texas Health Science Center at Houston President James T. Willerson, M.D., with collaborators at the Texas Heart Institute at St. Luke’s Episcopal Hospital, will lead one of the nation’s first clinical trials of stem cell therapy for heart failure patients.
At a March 23 news conference at Texas Heart Institute (THI), Willerson joined Emerson Perin, M.D., Ph.D., director of New Cardiovascular Interventional Technology at THI; Yong J. Geng, M.D., Ph.D., director of the UT Medical School’s Center for Cardiovascular Biology and Atherosclerosis Research; and Edward T. H. Yeh, M.D., director of the Research Center for Cardiovascular Disease at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, to announce that the U.S. Food and Drug Administration has approved the clinical trial.
“We are very excited about the FDA approval to begin this work in the Texas Medical Center at the Texas Heart Institute and St. Luke’s. We believe stem cell therapies will find a very important place in the future treatment of patients with heart and vascular disease,” Willerson said.
Willerson is an active clinician, researcher and educator in addition to his role as president of the most comprehensive academic health center in Texas. He holds the Edward Randall III Chair in Internal Medicine and is the Alkek-Williams Distinguished Professor. He also is chief of cardiology at St. Luke’s Hospital, as well as chief of cardiology and medical director of the Texas Heart Institute.
The Houston study builds on earlier research by Willerson, Perin, Geng, and Hans Dohmann, M.D., and his colleagues at the Pro-Cardiaco Hospital in Rio de Janeiro. The Brazil clinical trial involved 21 patients suffering from severe heart failure.
Perin threaded a special catheter through an artery into the patient’s left ventricle (the heart’s main pumping chamber) and mapped specific areas of muscle damage. He then used the catheter to inject stem cells derived from the patient’s bone marrow into the damaged heart muscle. Two million stem cells were injected in 15 sites for a total of 30 million stem cells in each patient. The same procedure will be used in Houston.
After two months, the hearts of the treated patients in Brazil had significantly less failure and pain, and were more able to pump blood than those of the untreated patients. The treated group also tended to do better on treadmill tests. At four months, the treated patients had a sustained improvement in their hearts’ pumping power and ability to supply blood throughout the body. None of the treated patients had serious problems such as sustained irregular rhythms, heart attack or death during or soon after the procedure.
The first phase of the THI study, which involves six patients, is designed to test for safety. After the FDA approves that phase, the study will focus on the efficacy of the treatment. In all, 30 patients will be randomized, with 20 receiving the stem cells. After six months of intensive follow-up observation, the 10 patients on placebos will be offered the opportunity to receive their own stem cells.
At this time the only approved treatment for severe heart failure – a progressive weakening of the heart due to cardiovascular disease – is a transplant. Not all patients are eligible for transplants, and the number of patients far outstrips the number of hearts available for transplant.
If stem cell injection is shown to work, Willerson said, it would be a relatively inexpensive therapy. Also, there would be no need for immunosuppressive drugs to prevent rejection, because patients are injected with their own cells. “This therapy would be generally applicable around the world,” Willerson said.
“We are encouraged and optimistic about it, but we will have to see how this clinical trial goes,” Willerson said.
Stem cells are capable of dividing and renewing themselves for long periods and of turning into other types of specialized cells. Embryonic stem cells have the greatest potential for this differentiation into other cells. Willerson and Perin are using only adult stem cells.
The exact mechanism by which the injections work is unknown, Willerson and Perin said, but they offered several possible explanations. The bone marrow stem cells could be creating new blood vessels; they might stimulate stem cells in the heart muscle to create new muscle; they might encourage muscle growth by bathing the affected areas with growth factors; or they might be turning into new muscle cells.
Willerson noted research has shown that injecting stem cells found in human blood into the left ventricles of mice resulted in some of the stem cells differentiating into heart muscle cells, smooth muscle cells and cells that line blood vessels. The lead author of that paper was Yeh, who also is chairman of the UT M. D. Anderson Cancer Center Department of Cardiology.
Trail-blazing research in an animal model that built the basis for the human clinical trials was led by Geng, who also is director of the Heart Failure Laboratory at the Texas Heart Institute. Geng continues his research on human stem cells.
Yeh and Geng also hold faculty appointments at the UT Graduate School of Biomedical Sciences at Houston.
— Scott Merville, Public Affairs