News Release

UofL awarded $9.56 million to form first-ever multicenter cardiovascular research network

UofL-led consortium includes Johns Hopkins, Emory and VCU to study cardioprotective therapies

Grant and Award Announcement

University of Louisville

LOUISVILLE, Ky. – The National Heart, Lung and Blood Institute has awarded $9.56 million over five years to a University of Louisville Health Sciences Center research scientist to form a multi-center network examining cardioprotective therapies at the preclinical level.

Dr. Roberto Bolli, director of the Institute of Molecular Cardiology and chief of the Division of Cardiovascular Medicine at UofL, is principal investigator of the "CAESAR Project" – a consortium for preclinical assessment of cardioprotective therapies that will involve laboratories at UofL, Johns Hopkins University in Baltimore, Emory University in Atlanta and Virginia Commonwealth University in Richmond.

The four-center project marks the first time the National Institutes of Health has funded a network of laboratories to test cardioprotective therapies at the preclinical level using the same scientific rigor as applied in clinical trials.

The multi-center network being established will be available to all investigators in the nation so that data can be shared with the goal of ultimately translating this type of basic research into clinically applicable therapies for patients with acute myocardial infarction, Bolli said.

Specifically, the researchers will perform blinded, randomized animal studies to examine how to lessen the damage done to heart muscle in a heart attack. An estimated 1.3 million Americans have a myocardial infarction – a heart attack – each year. The prognosis of these patients is dependent upon the size of the infarct – the larger the infarct, the greater the likelihood of subsequent heart failure and death. Also, the damage done to the heart is irreversible; once heart muscle is lost to an infarct, it is dead tissue that cannot be reclaimed.

For almost 40 years, the NIH/NHLBI has invested considerable resources in preclinical studies aimed at developing infarct-sparing therapies. Throughout this time, hundreds of therapies have been developed that have been claimed to limit infarct size in preclinical models. However, Bolli said, none have advanced to the clinical stage.

"This enormous investment – at least several hundred million dollars – over the past 40 years has not produced any notable clinical application. Results have generally not been replicated in from one lab to another, and no cardioprotective therapy is currently available for clinical use," Bolli said. "Approximately eight years ago, I began talking with NIH representatives about the need to change how we are conducting cardioprotective preclinical studies. Those conversations have led to this grant."

One key change in how these studies are conducted is the addition of a statistician in developing the research study design. Another is ensuring reproducibility; each study will be performed in two centers using identical protocols, with each center unaware of the other's results.

The goal of the project is to identify therapies that are proven to work through rigorous study in preclinical models and ultimately advance them to clinical trial stage.

"CAESAR will be a major paradigm shift in cardioprotection. By screening promising therapies and identifying those that are truly effective in relevant experimental models – and thus, are most likely to be ultimately effective in patients – CAESAR will focus clinical trials on those therapies and will dramatically advance our ability to rationally translate basic findings into clinical trials," Bolli said.

"Dr. Bolli's career continues to be distinguished by his efforts to develop innovative solutions for fighting heart disease, the leading cause of death in the United States," said Dr. James R. Ramsey, president of the University of Louisville. "By conceiving, creating and leading this network Dr. Bolli demonstrates daily how the people at the University of Louisville strive to find ways to improve the lives of people in Kentucky and beyond."

Joining Bolli in the research at UofL are Dr. Xian-Liang Tang, associate professor of medicine, Dr. Yiru Guo, associate professor of medicine, Dr. Qianhong Li, assistant professor of medicine, and Dr. Steven Jones, associate professor of medicine, all with the Division of Cardiovascular Medicine in the Department of Medicine; and Dr. Maiying Kong, associate professor of bioinformatics and biostatistics in the School of Public Health and Information Sciences.

Leading the efforts at the other university centers are Dr. Charles Steenbergen at Johns Hopkins; Dr. David Lefer and Dr. Jakob Vinten-Johansen at Emory; and Dr. Rakesh Kukreja at Virginia Commonwealth.

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