Researchers at Johns Hopkins have begun what is
believed to be the first clinical trial in the United
States of adult mesenchymal stem cells to repair muscle
damaged by heart attack, or myocardial infarct.
The so-called Phase I study is designed to test the
safety of injecting adult stem cells at varying doses in
patients who have recently suffered a heart attack. An
estimated 7 million Americans alive today have suffered at
least one heart attack and so are at greater risk for
chronic heart failure, sudden cardiac death or another,
potentially fatal, heart attack.
"This is an important milestone on the journey to
better cardiovascular care and to realization of the
promise of adult stem cell research," said lead study
investigator and cardiologist Joshua Hare, professor in the
School of Medicine and its
Heart Institute.
"Current approaches to cardiovascular disease can
prevent heart attack or alleviate its aftereffects, but
they have not included repair of damage that leaves sizably
dead portions of heart tissue as dangerous scars in the
heart," said study co-investigator and cardiologist Steven
Schulman, professor in the School of Medicine and director
of the coronary care unit at The Johns Hopkins Hospital.
Previous research in animals showed that when adult
stem cells were injected directly into the heart muscle,
heart function was restored to its original condition
within two months. Last November, at the American Heart
Association Scientific Sessions 2004, the Johns Hopkins
team showed, again in animal studies, that more than 75
percent of dead scar tissue disappeared after therapy,
which produced mostly healthy, normal-looking heart tissue
and left only a small trace of the heart attack.
The Phase I study is being conducted at Johns Hopkins,
with support from Baltimore-based Osiris Therapeutics,
which developed the stem cell product. The study will
involve 48 adults who have had their first heart attack
within 10 days of enrollment in the trial. All patients
will have been stabilized before acceptance to the trial,
and will have undergone cardiac catheterization and
ultrasound echocardiography to check that their main
coronary vessels are clear of blockages that may
precipitate another heart attack.
Eligible candidates must be able to safely travel to
Hopkins Hospital, be referred by a physician, be between 21
and 85 years old and have no pre-existing heart condition
that has been treated or requires treatment during the
study period.
Upon acceptance in the study, patients will be
randomly assigned to one of four groups, each made up of 12
patients who will receive a preset dose of stem cell
therapy or placebo. The study is double blinded, with
neither researchers nor patients aware of who received stem
cells until the Phase I study ends, six months after the
last patient has enrolled.
After injecting stem cells taken from the bone marrow
of an adult human donor into the subject's bloodstream, the
researchers will monitor the patient's progress for two
years to ensure that he or she safely tolerated the
infusion, determine any side effects and assess any
differences in the three doses under study, each involving
millions of adult stem cells. Study participants will spend
four days immediately after the procedure in the hospital
and will return for preset checkups, monthly for the first
three months and again after six months, 18 months and 24
months.
Magnetic resonance imaging studies, to show the size
of the area of heart muscle scarred by the infarct and
gauge the organ's ability to pump, will be conducted at the
beginning and end of the study as a measure of heart
function. Conclusive results will be available only when
and if Phase II and Phase III clinical trials proceed.
The Johns Hopkins team expects that after injection,
the adult stem cells will migrate to the damaged areas of
the heart muscle, responding to chemical signals released
by the heart after an infarct that triggers a repair
response from the bone marrow.
Related clinical research under way in China also uses
adult stem cells, but the cells come directly from the
patient and no universal donor is used, as in the Hopkins
study.
It remains unclear from earlier animal studies how or
why the adult stem cells develop into new and healthy heart
tissue, or exactly how long their healing effects last.
Adult stem cells are being used because they are
readily available from the bone marrow, where they are
plentiful. A special kind of bone marrow stem cell, called
a mesenchymal stem cell, was separated from other kinds for
use in this study. While their precise biological action is
not known, mesenchymal bone marrrow stem cells are known to
give rise to a variety of cell types, including bone,
cartilage, fat and other kinds of connective tissue cells
such as those in tendons, as well as muscle, such as the
heart. A stem cell is a special type of body cell that
gives rise to other types of specialized cells.
"Using mesenchymal stem cells also avoids potential
problems with immunosuppression, in which every human's
immune system might attack stem cells from sources other
than itself," Hare said. "Because they remain in an early
stage of development, mesenchymal stem cells do not trigger
an immune response, unlike what would happen if more
developed stem cells were used.
"While the bone marrow adult stem cells do not have
the same potential to develop into different organ tissues
as do embryonic stem cells, the use of adult stem cells in
this study shows their tremendous potential in developing
effective therapies for heart disease, and avoids the
controversy surrounding destruction of embryos to obtain
the embryonic variety," he added.
"Among its many benefits are that adult stem cells are
readily available from a number of donors and grow in large
quantities in the lab. In our experiment, the treatment
regimen is relatively simple, requiring only injection."
Funding for the study is provided by Osiris
Therapeutics, which developed the process for preparing the
adult mesenchymal stem cell product in use in the study.
Additional funding comes from Johns Hopkins' General
Clinical Research Center, its Institute for Cell
Engineering and the Donald W. Reynolds Cardiovascular
Clinical Research Center at Johns Hopkins. Other
investigators in this research are Stuart Russell, Ilan
Wittstein, Gary Gerstenblith, Alan Heldman, Joao Lima and
Kathy Wu.
According to the latest statistics from the American
Heart Association, in 2002, there were an estimated 565,000
new cases of heart attack in the United States, plus an
additional 300,000 cases of recurrent heart attack. Almost
180,000 of all heart attacks were fatal. The AHA also
estimated that 7,100,000 Americans had suffered at least
one heart attack. People who have had a heart attack have a
sudden death rate that is four to six times greater than in
the general population. About two-thirds of heart attack
patients do not make a complete recovery; however, 88
percent of those under age 65 are able to return to
work.
Study inclusion criteria can be found at
www.hopkinsmedicine.org/Press_releases/2005/
StudyInclusionCriteria.html.
Physicians interested in referring patients should
call 410-955-1160 for further information.
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