At first, 42 year-old heart attack victim Rodrigo Meraz wasn’t sure he wanted to participate in a groundbreaking clinical trial involving a new cell-based therapy to repair injured heart muscle at The University of Texas Medical School at Houston. But, he’s glad he did now.
Meraz, one of 53 patients in the
study, does not know if he received
an intravenous infusion of stem
cells or placebo, but he says he’s
feeling stronger these days and has
returned to one of his favorite
jogging trails inside Houston’s
Loop 610. Patients enrolled in the
study received an intravenous
i infusion of either stem cells or
placebo and neither patients nor
their physicians know whether or
not they received the stem cell drug.
Developed by Osiris Therapeutics, Inc., the cell-based therapy involves the use of adult mesenchymal stem cells to repair injured heart muscles, also known as the myocardium. The therapy is called Provacel and is in the preliminary stages of patient trials.
At a March meeting of the American College of Cardiology in New Orleans, organizers of the two-year clinical trial announced positive six month results which included fewer arrhythmias, improved heart and lung function, and improvement in overall condition. The Medical School is one of 16 clinical sites and the only site in the Texas Medical Center.
While he cannot be sure he received the stem cells, Meraz, a sales director, is convinced the stem cells are at work in his body, repairing his injured heart muscle - 40 percent of which was injured during his 2006 Valentine’s Day heart attack near Houston’s Galleria. “I feel better than ever,” he says.
For purposes of the study, Provacel must be administered within 10 days of a heart attack and Meraz waited until the last minute to make his decision. It was only after learning more about the regenerative nature of stem cells that he decided to go ahead with the treatment.
Meraz, the father of an 8-year-old son named Sebastian, considers himself lucky to be alive. Paramedics told Meraz that he “flatlined” while they were attending to him in the pharmacy store parking lot where he had initially sought treatment for heartburn. “I actually saw a bright light. I thought I was gone,” says Meraz, who was rushed to Memorial Hermann - Texas Medical Center, where he was treated for an acute heart attack.
Unlike many cell-based therapies, which utilize the patient’s own cells, the cells in Provacel come from healthy donors, an Osiris official says. In addition, the cells can be stored at an emergency center until needed.
Affecting 1.1 million Americans every year, heart attacks are caused by disruptions to the heart’s blood supply. Muscle cells can die within minutes of the blood being reduced or cut off. And, the body has a limited capacity to regenerate new heart muscles and repair wounds to the heart.
Ali E. Denktas, M.D., principal investigator for the Provacel study at the UT clinical site and assistant professor of cardiology, says cell-based therapies including Provacel appear to work but researchers are not sure why.
“Studies with acute myocardial infarction (heart attack) show that if you give cells of some sort to the heart relatively quickly, five to 10 days after the heart attack, they nest themselves in the heart and the heart improves. But, why it improves is debatable,” Dr. Denktas says.
Between 1 to 2 percent of the adult mesenchymal stem cells make their way to the injured heart, Dr. Denktas says. “There is a homing signal in your heart and it attracts the cells,” he says. “The other cells go to other parts of the body.”
While not as versatile as embryonic stem cells, some adult stem cells can differentiate or become specialized cells under the right circumstances. Mesenchymal stem cells are particularly versatile and can develop into muscle, bone, cartilage, or tendon.
Mesenchymal stem cells, according to the trial’s co-investigator Yong-Jian Geng, M.D., Ph.D., may revitalize scarred heart muscle and improve blood flow.
Dr. Geng, professor of medicine and director of the Center for Cardiovascular Biology and Atheriosclerosis Research, is no stranger to this type of work with four pending utility patent applications describing stem cells technologies to his name.
Dr. Geng did the preclinical research in acute myocardial infarction animal models to test stem cells donated by others beginning in 2001 – work supported by the Texas Technology Transfer Program in collaboration with Osiris.
“Little is known about the roles for stem cells in functional recovery even though some morphological studies indicate the stem cell contribution to regeneration of the arterial wall with atherosclerosis and mechanical injury,” Dr. Geng says.
Dr. Geng says many questions remain to be answered about cell-based therapies and heart disease, including whether additional cells will have to be administered throughout the patient’s lifetime, which type of cells are best, and what is the best way to administer them.
For years, scientists at the UT Health Science Center and the Texas Heart Institute at St. Luke’s Episcopal Hospital have been at the forefront of cell-based therapies for heart disease.
Initial work focused on the use of the patient’s own cells to treat chronic conditions, such as congestive heart failure – in which the heart can’t pump enough blood to the body’s other organs. The latest work involves cells donated by others and focuses on acute conditions like an acute heart attack.
In 2004, UT Health Science Center at Houston President James T. Willerson, M.D., with collaborators at the Texas Heart Institute, led one of the nation’s first clinical trials of stem cell therapy for heart failure patients.
In 2003, Dr. Willerson, Emerson Perin, M.D., Ph.D., director of New Interventional Cardiovascular Technology at Texas Heart Institute, Dr. Geng, and colleagues reported on the initial study done with cell-based therapy for patients with severe heart failure with direct transendocardial injections of bone marrow-derived mononuclear cells into the heart conducted in Rio de Janeiro, Brazil.
Dr. Perin injected stem cells derived from the patient’s own bone marrow into the damaged heart muscle. After two months, the hearts of the treated patients in Brazil had significantly less failure and pain and were more able to pump blood than those of the untreated patients.
“Drs. Perin and Willerson are pioneering the use of cell-based therapies to treat heart disease,” Dr. Denktas says.
Drs. Willerson, Geng, and Perin, in an editorial in Circulation Research, wrote that, “The initial results of treating acutely and chronically infarcted human hearts with stem cells are encouraging, but much remains to be done. A better understanding of the mechanisms responsible for improved myocardial blood flow and function with cell-based treatment is needed.”
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