April 1, 2005
Can Stem Cells Reverse Heart-Attack Damage?
Therapy might revolutionize treatment of heart patients
HealthDay News -- Joel Parran, a 61-year-old dentist from Maryland, suffered a heart attack March 19 while working out at his local gym.
He was rushed to Johns Hopkins Hospital in Baltimore, where he underwent heart surgery, which included the insertion of four stents into his narrowed arteries. An otherwise fit and healthy man, Parran was on his way to a swift recovery from the operation.
But then the doctors asked Parran if he'd be willing to take part in a milestone medical experiment -- an infusion of adult stem cells from donor bone marrow that might possibly reverse damage to his heart tissue caused by the attack.
"I gave it a lot of consideration," Parran said. "To be honest, I never thought of this as a life-or-death situation, but if there was a chance of this being successful, if I did get the stem cells, it might regenerate some of the muscle tissue, and I thought, 'What do I have to lose?' "
After a work-up that included a pulmonary breathing test, a CT scan and an MRI, the doctors gave Parran an intravenous infusion of the cells, a procedure he said took about seven minutes. He remained in the hospital for four days while doctors monitored his condition.
Now, two weeks after his ordeal began, Parran is back at work, treating his own patients and showing no side effects except itching caused by one of the drugs he was given during his heart surgery.
And while his doctors are not attributing Parran's recovery to the stem cell therapy, they are hoping that proof will emerge within six months that the treatment helped to repair any damaged heart tissue.
Parran is the first patient to take part in the Hopkins study now under way that, doctors say, could significantly change the direction of cardiac care. Instead of just managing the ill effects of a heart attack, as happens now, the researchers hope to create a new approach that actually would repair heart muscle damaged by a heart attack.
It is believed to be the first clinical trial in the United States of adult mesenchymal stem cells to repair muscle damaged by a heart attack, according to the Hopkins researchers. Mesenchymal stem cells are those that give rise to skin, muscle, bone and cartilage.
"It is incredibly exciting for us after studying cardiac repair to be now finally starting the study. This could revolutionize the way heart attacks are treated," said study leader Dr. Joshua Hare, a professor of medicine and biomechanical engineering at the Johns Hopkins University School of Medicine and Heart Institute.
"We are actively enrolling and eager to take patients in this Phase I safety study," he added.
By infusing a specific type of donor adult stem cells into the blood of recent heart attack victims, the Hopkins doctors hope to replicate animal studies in which injected stem cells matured and replaced scar tissue that had developed after a heart attack with healthy new heart tissue.
The study is open to men and women between the ages of 18 and 85 who have had one heart attack. One caveat: They must be available for the stem-cell therapy at Johns Hopkins School of Medicine within 10 days of their heart attack.
"This field is still very young but potentially could offer a very, very large clinical benefit," said Dr. Warren Sherman, director of the Cardiac Catheterization Laboratory at Mount Sinai Medical Center in New York City. "Three areas are being actively investigated: Is there any kind of cell that is going to help the patient; when is the best time to give it, and what mechanism can be used to deliver it."
Sherman said other work in the field includes harvesting a heart attack victim's own stem cells for use in repairing heart muscle, and injecting stem cells directly into the heart muscle.
In earlier animal experiments at Hopkins, Hare and his colleagues found that mesenchymal stem cells, when introduced into the blood stream, migrated to the site of heart tissue that had been damaged by a heart attack. Once there, they matured, replacing the dead scar tissue with mostly healthy, normal-looking heart tissue that left only a small trace of heart attack damage.
"The muscles seem to be amenable to stem cell growth," Hare said. In pigs, he added, scar tissue was reduced by 50 percent within two months of injection of the stem cells.
Hare hopes to see similar results in the human study within three to six months.
Mesenchymal stem cells are found in the bone marrow of adult humans and have the potential to develop into mature cells that produce fat, cartilage, bone tendons and muscle. Because they are in an early stage of development, they don't trigger an immune response when placed in someone else's body, the researchers said.
The Phase I, double-blind study at Johns Hopkins is being done with support from Baltimore-based Osiris Therapeutics, which developed the stem cell product.
Hare said the first part of the trial will be a safety phase, to study the dosages and measure cardiac improvement. That's why the study is restricted to people who have no heart disease prior to the attack that brings them into the study.
"If patients get the cells when the injury is occurring, the potential benefit is the greatest," he said. "If we get through this safety phase, then we will be on to experiment with therapies for people with existing heart disease."
Hare said there will be four groups in the study. Within each group of 12 people, one-third will receive a placebo and the remaining two-thirds will get a dose of the stem cells.
All the participants will be monitored for two years to ensure that the doses are safely tolerated, to determine the different responses to different levels of doses and to determine any side effects. An MRI at the beginning and end of the study will let doctors see how much of the diseased heart muscle has been repaired and measure heart function.
If the Phase I trial shows the treatment to be safe, doctors will continue with Phase II and Phase III trials, which, if successful, could lead to the therapy becoming available to the general public.
As for Parran, he said, "I feel a little special, unique, being the first one. But the pros outweigh the cons, and there may have been some altruism involved -- if it helps me and it helps someone else, that's all to the good."
"I hope I don't get morphed into Dracula," he added.
For more on how the heart works, visit the American Heart Association.