Heart specialists at the
Johns Hopkins Heart Institute have been awarded more
than $12 million from the National Heart, Lung and Blood
Institute 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 a new federal
program focused on cell-based therapies that could be ready
for clinical trials testing within two years, the agency
says. Johns Hopkins is one of only three centers initially
funded as a Specialized Center for Cell-Based Therapy for
Heart, Lung and Blood Diseases, or 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," Eduardo Marban, professor and
chief of
cardiology at the School of Medicine and its Heart
Institute, said.
"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 said.
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 which has
already begun clinical trials. The second 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 Marban,
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 Marban'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. 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," Hare said.
Richard Lange, chief of clinical cardiology at
Hopkins, who leads research efforts into ischemic heart
disease and adult congenital heart disease, said, "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.
Marban 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. 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.