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Temple Researchers Receive $11.6 Million to Study Ways to Reduce Heart Attack Damage
Scientists at Temple University School of Medicine have been awarded a five-year, $11.6 million grant from the National Heart, Lung and Blood Institute of the National Institutes of Health to develop new approaches to prevent, slow or reverse damage to the heart after a heart attack.
"The overall goal of the grant is to try to develop novel therapies to enhance the heart's recovery after a heart attack," said Steven R. Houser, PhD, Professor and Chair of the Department of Physiology and Director of the Cardiovascular Research Center at Temple University School of Medicine, who leads the overall program project grant.
Dr. Houser explained that typically after a heart attack, a patient may be treated and sent home after a period of time to recover. Over the next few weeks, the part of the heart that was deprived of oxygen during the heart attack mostly dies, and the damaged heart eventually changes its shape and size, remodeling itself to compensate, becoming less efficient. "We really haven't done anything yet to intervene to reduce the injury and enhance regeneration and repair in the area of the heart that died," said Dr. Houser. "That's our goal in this project."
The program project consists of three individual research projects and four supporting core areas, including surgery and therapeutic intervention, cell and tissue evaluation, gene therapy and administration. Investigators in each project will evaluate a unique drug or therapy in a number of both laboratory and animal models that represent the heart after a heart attack or the heart that is remodeling after injury. "The program project grant is an opportunity for researchers at Temple to rapidly move from discovery in the laboratory to translation into potential therapy," Dr. Houser said.
In one project led by Dr. Houser, his team will examine ways to block excess calcium from entering areas in the heart muscle cells that house molecules that drive harmful remodeling, with the hope that this will lessen heart damage and reduce the likelihood of death after a heart attack.
According to Dr. Houser, while the level of calcium in the heart muscle cell plays a role in determining how strong the heart contracts, too much calcium can be dangerous. He and his co-workers have found calcium channels that separately affect the heart's ability to contract and its potentially harmful remodeling after a heart attack. They have evidence in laboratory experiments that they can block the excessive influx of calcium and halt the remodeling process, without affecting contractions, and his group's research is aimed at proving this can be done in more complex animal models. They will also test the use of gene therapy in delivering this blocking agent.
Another group led by Walter J. Koch, PhD, Professor and Chair of the Department of Pharmacology at Temple University School of Medicine and Director of Temple's Center for Translational Medicine, is studying GRK2 (G-protein coupled receptor kinase 2), a type of enzyme that regulates signaling in the heart, and more specifically, helps control the activity of proteins that regulate the force and speed of contraction. The system doesn't work properly in heart failure; GRK2 activity is increased, resulting in improper signaling.
Dr. Koch will study potential therapies to restore GRK2 to normal and improve heart function, and will also try to determine whether inhibiting GRK2 promotes heart regeneration. He and his colleagues plan to test the use of gene therapy after a heart attack in reversing the effects of chronic heart failure – a prelude, they hope, to a clinical trial.
A third project, led by Jeffrey Molkentin, PhD, Professor of Pediatrics at the Cincinnati Children's Hospital Medical Center and a Howard Hughes Medical Institute investigator, focuses on a molecular protein switch called protein kinase C (PKC), which goes into overdrive in heart failure. Researchers have shown that PKC is hyper-activated when the heart is undergoing remodeling after a heart attack, and Dr. Molkentin's group plans to test an agent that may be able to reduce PKC activity to see if this in turn will reduce the likelihood of heart cell death.
Dr. Houser sees all of these approaches as extremely promising. "If we can get data in these preclinical models we're developing," he said,"we're hoping that within five years we will have new trials and novel therapies to help people with heart attacks."
Date Published: Friday, August 17, 2012
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