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$11.6 Million Grant Boosts Study of Often-Fatal
Aortic Diseases
Researchers in multi-institutional center stalk a stealthy killer
that is the 15th leading cause of death in the United States
A new, $11.6 million research grant will speed the hunt of Dianna Milewicz, M.D., Ph.D., and others who are seeking the genetic causes and new treatments for a stealthy disease that kills people in the prime of their lives.
Dianna Milewicz, M.D., Ph.D.,
professor at the
UT Medical
School at Houston, is lead
investigator
and director of a
new
center that will seek
genetic
causes
and new treatments for
aortic
diseases.
Photo by Ester Fant
The five-year grant from the National Heart, Lung and Blood Institute (NHLBI) will create the Specialized Center for Clinically Oriented Research in Thoracic Aortic Aneurysms and Dissections, to be located in the Texas Medical Center.
Milewicz, professor and director of the Division of Medical Genetics at The University of Texas Medical School at Houston and holder of the George H. W. Bush Chair in Cardiovascular Research, is lead investigator and director of the multi-institutional center.
“This is a first step toward understanding the disease process leading to aortic aneurysms and dissections, so we can go after better biomarkers, better imaging and better ways to predict outcomes,” said Milewicz, who has extensively researched the genetic basis of thoracic aortic aneurysms and dissections. “The ultimate goal of the grant is to prevent premature deaths due to aortic dissection or rupture and hopefully lead to new therapies to treat the disease.”
Main Blood Vessel from the Heart
The aorta is the main blood vessel leading out of the heart. It supplies blood to the rest of the body. Some people develop a progressive degeneration of the aortic wall, leading to a bulging aneurysm, or to a dissection (a tear in the wall). Thoracic aneurysms tend to be without symptoms until a catastrophic dissection or rupture occurs.
“We don’t know the pathology of the aortic wall degeneration,” Milewicz said. “Understanding the pathological process is crucial in order to develop new therapies and diagnostic tools for the disease. The proposed projects in the grant work toward those goals.” Milewicz also holds faculty appointments in the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases and the UT Graduate School of Biomedical Sciences.
Other participating institutions are Baylor College of Medicine and the UT Medical Branch at Galveston (UTMB). Along with the UT Medical School, major sites for patient recruitment and research are Memorial Hermann Hospital-Texas Medical Center, the Texas Heart Institute at St. Luke’s Episcopal Hospital and Texas Children’s Hospital.
Co-directors of the center are Hazim Safi, M.D., professor and chairman of the Department of Cardiothoracic Vascular Surgery at the UT Medical School at Houston, and Joseph Coselli, M.D., professor and chief of the Division of Cardiothoracic Surgery at Baylor College of Medicine.
“This award represents an opportunity for us to link decades of surgical research and management to basic sciences that address the fundamental biology of aortic disease,” Safi said. “An NIH-funded effort of this scope is unprecedented in this area of research, and we hold great hope that new findings will lead to rapid development of new therapies.”
Up to 20,000 Deaths a Year
Thoracic aortic disease is the 15th leading cause of death in the United States, killing up to 20,000 people a year. Famous victims include actor John Ritter (54 years old when he died) and the creator of Broadway hit “Rent,” Jonathan Larson (who was 35). Untreated high blood pressure and smoking also can lead to the disease in people predisposed to it.
Emergency room doctors unfamiliar with its symptoms sometimes mistake a dissection as a flu virus or muscle pains. Once the aorta begins to dissect, patients may have anywhere from minutes to hours before it ruptures. Even if properly diagnosed, emergency surgery to repair the dissection is risky.
But if caught early enough, when an aneurysm is five centimeters or less, a surgical procedure to replace the diseased portion with a Dacron graft has a high degree of success.
“This critically important work effectively builds upon the leadership role the Texas Medical Center has taken in the successful surgical management of aortic pathology, aneurysms and dissection,” co-director Coselli said. Michael E. DeBakey, M.D., chancellor emeritus of Baylor College of Medicine, and Denton A. Cooley, M.D., president of the Texas Heart Institute and clinical professor of cardiothoracic and vascular surgery at the UT Medical School, pioneered successful surgical repair in the late 1950s.
Genetics of Aortic Disease
“Research programs (in the new center) are focused on the genetics of aortic disease, and the imaging and management of patients with known problems or familial proclivity,” Coselli said. “They will allow for earlier diagnosis, as well as significantly improved management, thus reducing morbidity and mortality. Ultimately genetic pathways hopefully make prevention entirely possible.”
Researchers including Milewicz have identified some of the defective genes that cause the inherited form of the disease, which affects 20 percent of people with aneurysms and dissections. Through DNA testing on family members, early identification of those at risk has led to diagnostic imaging and ultimately to saving lives.
“We’ve come a long way,” Milewicz said. “We’ve identified and mapped genes over the years and have a very well-established research program looking at the genetic basis for this disease. In addition, we have begun to understand how you use that information to manage the disease. We want to take it one step further and discover the biological pathways to this disease, whether it’s people who carry mutated genes or those who don’t but still end up with this disease.”
“The center takes advantage of the Genome Center at Baylor and the studies they have done there. Galveston has very talented investigators who are participating in one of the projects, plus they have a state-of-theart proteomic center also involved in the grant,” Milewicz said. “We will also be training the next generation of physician-scientists to understand this disease and carry on the research for years to come.”
James T. Willerson, M.D., president of The University of Texas Health Science Center at Houston and president-elect of the Texas Heart Institute, will chair the Internal Advisory Committee.
For descriptions of the specific research projects, see http://publicaffairs.uth.tmc.edu/distinctions/archive/2006/ September/aortic.html.
By Deborah Mann Lake, Public Affairs