National funding goes to Johns Hopkins to advance research on stem cell therapies for heart attack

September 29, 2005

Heart specialists at Johns Hopkins Heart Institute have been awarded more than $12 million from the National Heart, Lung, and Blood Institute (NHLBI) to study how stem cell therapies can be used to treat hearts damaged by heart attack or heart failure.

The five-year NHLBI funding is part of new federal program focused on cell-based therapies that could be ready for clinical trials testing within two years, the agency says. Hopkins is one of only three centers initially funded as a Specialized Center for Cell-Based Therapy for Heart, Lung and Blood Diseases (SCCT), and is the only center dedicated to new therapies for heart problems.

"This special grant strengthens the federal government's commitment to advanced medical research in the United States and it shapes the next chapter on Hopkins' historic role in cardiology," says Eduardo Marbán, M.D., Ph.D., professor and chief of cardiology at The Johns Hopkins University School of Medicine and its Heart Institute.

"The era of cardiac surgery was pioneered at Hopkins with the 'blue-baby' operation in the 1940s, and now we have the honor of continuing in this tradition by harnessing the next generation of therapies based on stem cells," he adds.

More than 30 Hopkins faculty and staff, including cardiologists, physiologists, radiology technicians and research nurses will be involved in the SCCT initiative, which will focus on two major projects. One of the five-year projects has already begun clinical trials. The second project continues with preclinical animal and laboratory research, required by the Food and Drug Administration before new therapies can be approved for initial testing.

The laboratory research group will be led by Marbán, whose team will study the potential of using a patient's own cardiac stem cells to repair heart tissue soon after a heart attack, or to regenerate weakened muscle resulting from heart failure, perhaps averting the need for heart transplants. By using a person's own adult stem cells instead of those from another donor, there would be no risk of triggering an immune response that could cause rejection.

The treatment concept is based on Marbán's recent success in replicating large numbers of cardiac stem cells in the lab within a very short time, as little as four weeks. The stem cells, extracted from healthy parts of hearts not otherwise damaged by heart attack, grew to form clusters, called cardiospheres, which contain cells that retain the ability to regenerate themselves and to develop into more specialized heart cells that can conduct electrical currents and contract like heart muscle should.

Directing the overall SCCT effort at Hopkins will be cardiologist Joshua Hare, M.D. Hare, a professor of medicine, leads the project to evaluate adult mesenchymal stem cells as a potential therapy to heal damaged hearts. Last year, his research in animals showed that stem cells harvested from one pig's bone marrow and injected into another pig's damaged heart restored heart function and repaired damaged heart muscle by 50 percent to 75 percent after just two months of therapy. In March 2005, Hare and other researchers began a Phase I clinical trial to test the safety of injecting adult stem cells at varying doses in patients who have recently suffered a heart attack. In total, 48 patients will participate in this study, which involves several sites across the country, including Hopkins. Results are not expected until mid-2006.

Because mesenchymal stem cells are in an early stage of development, they, too, avoid potential problems with immune rejection, in which every human's immune system might attack stem cells from sources other than itself. Bone marrow adult stem cells do not have the same potential to develop into different organ tissues, as do embryonic stem cells, whose use is more controversial.

"Ultimately, the goal is to develop a widely applicable treatment to repair and reverse the damage done to heart muscle that has been infarcted, or destroyed, after losing its blood supply," says Hare.

According to Richard Lange, chief of clinical cardiology at Hopkins, who leads research efforts into ischemic heart disease and adult congenital heart disease, "This is an incredibly exciting time to be working in cardiac care because we are at the forefront of some key medical breakthroughs, including research on a first-ever cure for heart attack in humans, a discovery that would change cardiac care as we know it today."

The American Heart Association recently estimated that there were 565,000 new cases of heart attack in the United States, plus an additional 300,000 cases of recurrent heart attack. More than 3 million Americans suffer from congestive heart failure, a common target of the myoblast stem cell therapy. Myoblasts are the stem cells found in muscles.
Marbán is also the Michel Mirowski, M.D., Professor of Medicine at Hopkins and director of its Donald W. Reynolds Cardiovascular Clinical Research Center and the Institute of Molecular Cardiobiology. Hare is also director of the cardiobiology section of Hopkins' Institute for Cell Engineering. And Lange is the E. Cowles Andrus Professor of Cardiology and associate director of the Research Center Training Program of the Donald W. Reynolds Cardiovascular Clinical Research Center.

Johns Hopkins Medicine

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