Stem cell researchers at the University of Miami Miller School of Medicine’s Interdisciplinary Stem Cell Institute are preparing to embark on another research milestone. Joshua M. Hare, M.D., professor of medicine and director of the Interdisciplinary Stem Cell Institute (ISCI), has received approval from the U.S. Food and Drug Administration to begin the first clinical trial in the nation comparing autologous stem cells to donor stem cells for patients with dilated cardiomyopathy, a condition that causes congestive heart failure and is a major cause of death and disability.
Dilated cardiomyopathy directly causes weakness of the heart muscle, a condition that can be very severe and lead to heart failure. It can be caused by viral infections, genetic disorders, inflammation or in many cases the cause is unknown. Patients are treated with medication which can sometimes improve heart function, but some patients’ hearts continue to deteriorate and require heart transplantation or other advanced therapies.
ISCI investigators are already studying a number of stem cell types in clinical trials for patients with heart muscle damage from a prior myocardial infarction (heart attack). This new study is the first to examine whether stem cells may also prove beneficial for other forms of heart muscle weakness, and will compare the effects of autologous cells (stem cells derived from a patient’s own bone marrow) with allogeneic cells (stem cells from an adult donor). Enrolled patients with dilated cardiomyopathy will be injected with either their own stem cells or cells from a pre-screened healthy donor.
“This trial will answer major questions about the treatment of heart failure, and could transform treatment of these patients,” Hare says. “Cell therapy for this condition could reduce the need for heart transplantation and other advanced therapies by providing a viable alternative. Also, using donor cells could make this potential new therapy highly practical and easy to deliver.”
While there is quite a bit of excitement about the potential healing ability of stem cells, Hare explains that there is also concern that stem cells taken from a patient who is already ill may be compromised and weakened because of that illness. “This study will help us find out if a heart failure patient’s stem cells are already damaged and not as effective. If so, the availability of donor cells could be life-saving to these patients.”
The ability to safely and effectively use a donor’s cells could also provide physicians with a nearly unending supply of these potentially healing cells. Using autologous cells is a time-consuming process. Physicians must first extract a patient’s bone marrow, containing mesenchymal stem cells. Once those mesenchymal cells are separated, they must be cultivated in a lab to enhance their numbers – a process that takes up to six weeks. For some heart failure patients, waiting that long for an effective treatment may not be feasible. “If we can prove that donor cells work as well or better than autologous cells without any negative side effects,” says Hare, “that will open up many new doors for us when it comes to new therapies.”
Currently, Hare is leading three other stem cell trials for patients with heart failure due to heart attack or myocardial infarction at the Miller School. The first, which began in April 2008, is a double-blind, placebo-controlled study in which doctors are injecting either the patient’s mesenchymal stem cells or a placebo into the heart during surgery. The two additional studies deliver cells to patients by catheter, avoiding a surgical procedure.
In the new clinical trial, dubbed POSEIDON–DCM, scientists will use one or two young, healthy donors who have been thoroughly screened for any communicable diseases. Once those donors are recruited, their cells can be cultivated in the lab to grow numerous batches for use in this trial. Mesenchymal stem cells are immunoprivileged, meaning there is no need for any matching process between the donor and the recipient. Immune suppressive drugs are not required, and rejection has not been seen in heart failure patients treated thus far with donor stem cells.
Alan W. Heldman, M.D., professor of medicine, leads the team that injects stem cells directly into the heart muscle. In the new POSEIDON–DCM trial, stem cell injections will be done with the NOGA® electroanatomic navigation system, which allows the cardiologist to guide injections into specific sites in the heart based on the electrical and mechanical function at that site. “In the other trials we’re conducting, we have already gained an enormous amount of experience with the techniques of injecting stem cells into patients’ hearts,” says Heldman. “This study may add tremendously to the state of knowledge about whether and how stem cells can truly help regenerate stronger heart muscle.”
Another key member of the ISCI team, Juan Pablo Zambrano, M.D., assistant professor of medicine, agrees that the study will provide a better understanding of the role of stem cells in cardiac repair. Zambrano hopes the trial will “show an option for an even larger heart failure population that suffers from conditions other than heart attacks.” He says the study will also expand their expertise in new imaging modalities that help locate weakened areas of the heart as targets for cell administration.
William O’Neill, M.D., executive dean for clinical affairs, describes this new trial as “another milestone for the University of Miami’s Interdisciplinary Stem Cell Institute.” He says Hare and his colleagues are taking a leadership role in stem cell therapy for heart disease, and the Poseidon-DCM trial will “further our understanding of which cells are most likely to repair damaged heart tissue.”
This trial is a key step forward for the team, says Ian McNiece, Ph.D., professor of medicine and director of experimental and clinical therapies at ISCI. “This study will provide important information relating to the types of heart disease that can be repaired by mesenchymal stem cells.”
The external scientific advisory board of ISCI recently concluded that the institute is the leading translational stem cell program in the U.S. and that the cohort of patients treated for cardiac disease is the largest in the nation. The board’s report said the “complement of trials being offered at UHealth broadens the availability of experimental therapy to patients and offers an alternative to the growing trend of medical tourism for cell based therapies.”
For more information about the Poseidon-DCM clinical trial, contact Darcy Velazquez, R.N., B.S.N, at 305-243-9106 or 786-427-5609.