Thursday, January 28, 2010
Investigational treatment may reduce inflammation and limit heart tissue injury
Heart experts used to think cardiac tissue damaged after a heart attack could not be repaired. That assumption is changing as more is learned about the properties of certain stem cells to grow or regenerate tissue, including heart muscle. University of Maryland physicians are collaborating with 41 centers in the United States and Canada in a two-year clinical trial of an investigational intravenous adult stem cell therapy. The therapy will be tested in patients who have had their first heart attack within the previous seven days.
This study is unique because it is testing cells that have been previously extracted and grown from healthy donors and are ready to be infused into the patient’s blood stream, just like an intravenous medication. Other stem cell therapies being studied elsewhere for heart attack patients use stem cells that are taken from the patient, grown in a lab for three-to-four weeks and then injected directly into the heart. This time delay may have a significant impact on the effectiveness of the therapy.
“After a heart attack, there is a lot of scar tissue and dead heart muscle. Much of that muscle is lost up front, right after the heart attack,” says Mark Vesely, MD, the principal investigator at the University of Maryland. “The body has limited ability to rebuild damaged heart muscle, but the goal of this study is to try to limit the amount of damage that is done by the heart attack and take advantage of a natural healing process,” says Dr. Vesely, assistant professor in the Department of Medicine at the University of Maryland School of Medicine and a cardiologist at the University of Maryland Medical Center.
Current treatments, such as catheterization and bypass surgery, can restore blocked blood flow to the heart, while drug therapy is designed to keep coronary disease from progressing and help the heart pump blood more effectively. Despite the success of these treatments, Dr. Vesely says they are not effective at restoring damaged cardiac muscle. He hopes this stem cell therapy will do just that.
The therapy uses what are known as mesenchymal cells, adult stem cells stored in bone marrow that can generate new tissue, including heart muscle and other muscle, and develop into other types of cells, including bone, cartilage, ligament, tendon and fat. Mesenchymal cells are part of the body’s complex healing system. They respond to chemical signals sent from inflamed parts of the body, such as a twisted ankle or knee.
Inflammation is part of the picture after a heart attack, says Dr. Vesely, so the heart, too, sends signals to the mesenchymal cells. “If you think of these stem cells as almost like a hound dog, they ‘pick up the scent’ and track down areas of inflammation,” says Dr. Vesely. Once the mesenchymal cells pick up the signals, they leave the bone marrow, travel through the blood stream to the site of the inflammation and begin their repairs.
Dr. Vesely says researchers are not sure how mesenchymal stem cells reduce inflammation and heal tissue, but it is clear that children have a great abundance of these cells. As people age, the number of available stem cells gets smaller and smaller, and their ability to change into different types of cells is reduced as well. But Dr. Vesely points out that several days after a child has fallen and scraped his knee, the wound is healed with no scar. “Children are not going to get scarring, because they are still growing. As we get older, our scar formation goes up, our inflammation goes up, while our regenerative ability goes down,” he says.
Most heart attacks occur in older people. “The idea behind this trial is this: if part of that loss of the healing process is because we have lost stem cells, let’s try to game the system, by supplying more of these stem cells to help the healing process,” says Dr. Vesely.
The mesenchymal stem cells in this study have been taken from bone marrow samplings of young, healthy adults in their twenties and not from a fetus, embryo or animal. The marrow is filtered so it yields only these specific stem cells, which are easily grown into large quantities. The cells are processed as an intravenous infusion and marketed as Prochymal, from Osiris Therapeutics, Inc., of Columbia, Md., sponsor of the study. Prochymal is an “off-the-shelf” product for immediate use without further preparation.
Mesenchymal stem cells are universally compatible, which means they can be used in anyone without typing or matching, similar to blood type O. Because of this quality, the cells have an extremely low chance of being rejected by the recipient’s body.
This research project is a multi-center, randomized, double-blind, placebo-controlled Phase II study evaluating the safety of Prochymal in 220 patients. Doctors and patients will not know who is receiving the active ingredient and who is receiving an inactive infusion (a placebo). Patients in the study will receive a single injection of Prochymal or the placebo within seven days of their first heart attack and will undergo a variety of heart function and imaging tests. It is expected that the infused mesenchymal cells will travel to the heart and all other areas of the body where there is swelling and inflammation. To help ensure that most of the cells go to the heart, the study will exclude people who have inflammatory diseases, such as rheumatoid arthritis.
In an initial Phase I cardiac trial involving 53 patients, there were few negative side effects, heart function improved, and cardiac arrhythmias (irregular heartbeat) were reduced in patients treated with Procyhmal compared to the placebo group.
“Stem cell research is part of our faculty’s continuing quest to find more effective treatments for diseases that challenge both physicians and patients alike,” says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and dean of the University of Maryland School of Medicine. “It is too early to know whether these infusible cells will work as predicted in large numbers of heart patients, but this research showcases the novel ideas and creative thinking that have positioned our stem cell researchers at the top of efforts that may help solve some of the greatest medical problems.”
According to the American Heart Association, heart disease is the single leading cause of death, responsible for one out of every six deaths in the United States. There are more than 1.2 million new and recurrent heart attacks each year. About 34 percent of people who experience a heart attack in a given year die from it.