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University of Cincinnati Academic Health Center
Publish Date: 09/16/02
Media Contact: AHC Public Relations, (513) 558-4553
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Researchers Study Genetics of Stroke with $30 Million in Grants

Cincinnati--Researchers at The Neuroscience Institute at the University of Cincinnati (UC) have secured a landmark $30 million in federal dollars over the past two months to probe the genetic underpinnings of stroke and to test new therapies for acute stroke.

The funding, which underwrites four separate genetic studies and two large clinical trials of acute stroke therapy, represents one of the highest totals ever awarded to UC researchers in a single medical area at one time and further cements UC's reputation as an international center of stroke and genetics research.

In the largest of the four genetic studies, the National Institutes of Health funded UC $15 million over the next five years to spearhead the Familial Intracranial Aneurysm (FIA) study. This international effort is designed to identify the genes that cause the development and rupture of brain aneurysms. The study involves 23 centers in North America, Australia and New Zealand and brings UC into collaboration with some of the world's preeminent institutions, including the Mayo Clinic and the National Human Genome Research Institute, and regional collaborators such as Indiana University. The kickoff for the FIA study will occur September 23-24 at the Kingsgate Marriott on the UC campus.

NIH has also funded UC to head two large multi-center studies of new treatments for patients with stroke who are seen within three hours of stroke onset. The first study is a $7 million program to develop new treatments and blood markers for patients with acute stroke, one of only two such programs awarded in the entire country. In this study, UC investigators and collaborators at six other U.S. centers will test combining lower doses of t-PA, the currently approved therapy for stroke, and another medicine, integrelin, which affects blood platelets. The start-up meeting for this study will also take place at UC on October 21-22.

The second stroke treatment study, funded by the NIH and EKOS Corporation, is the second phase of a study designed to test t-PA given in a vein, followed by t-PA and ultrasound energy delivered by a small tube or catheter at the site of the blocked brain artery. UC also leads this 13-center North American study, which recently completed its first phase this spring.

William Martin, II, MD, dean of the College of Medicine, notes, "UC's growing reputation as a world-class center for neurological research is due in large part to the outstanding cooperation of local hospitals and physicians and to the generosity of patients and families who have participated in these studies. Our success also reflects the outstanding collaborations between many scientists and physicians throughout the College of Medicine. For example, these studies involve the Departments of Neurology, Emergency Medicine, Neurosurgery, Radiology, Environmental Health and Biostatistics, the Institute for Health Policy Research and biostatisticians at Cincinnati Children's Hospital Medical Center."

The infusion of federal research dollars for genetic and treatment studies of stroke offer potential health benefits for families that have been touched by stroke. Parents, children and siblings from Greater Cincinnati and beyond are being recruited to participate in the stroke studies, with the hope that these new therapies and a better understanding of stroke's genetic links could make a real difference for the 700,000 Americans who have a new stroke every year.

The following is a list of the studies funded by the National Institutes of Health:

Genetic Studies:
The five-year, $15 million, NIH-funded FIA study is led by Joseph Broderick, MD, chair of the Department of Neurology. UC researchers are in the process of identifying 400 families in which two or more siblings or three or more family members have suffered a ruptured brain aneurysm.

A five-year, $5.2 million extension of the Genetics and Environmental Risk Factors for hemorrhagic Stroke (GERFHS) study. The study is examining the environmental causes (such as smoking) and their relationship to the genetic causes of bleeding into the brain and bleeding surrounding the brain due to ruptured intracranial aneurysms. More than 500 people with brain hemorrhage and 1,000 volunteers from the community of similar age, gender and race, who have not had a brain hemorrhage, have already been recruited from the region. Similar numbers of new patients and family members from Greater Cincinnati and Northern Kentucky will be recruited over the next five years.

The five-year, $668,000 Familial Aggregation of Stroke study, an investigation into the likelihood that a family member of a stroke victim will also suffer a stroke. Daniel Woo, MD, principal investigator and assistant professor of neurology, notes, "We want to learn why, in certain families, smoking seems to lead just to stroke, while in other families it leads to lung cancer or heart disease."

The five-year, Siblings With Ischemic Stroke Study (SWISS), which seeks to identify genes that may contribute to an ischemic stroke, a blockage of blood flow to the brain. Brett Kissela, MD, assistant professor of neurology and the site principal investigator for SWISS, is seeking sibling pairs who have suffered strokes and a third sibling who has not experienced a stroke.

Treatment Studies of Acute Stroke:
The five-year, $7 million Special Programs for Treatment of Acute Stroke (SPOTRIAS) is one of only two programs awarded by the National Institutes of Health in the country. Dr. Broderick is the overall principal investigator of the program. Arthur Pancioli, MD, associate professor in the Department of Emergency Medicine, heads the six-center clinical trial, called CLEAR, that will test lower doses of t-PA and integrelin, a new drug for stroke. Frank Sharp, MD, professor of the Department of Neurology, heads another study that will look at the gene responses in blood cells in patients with acute stroke, and Edward Jauch, MD, assistant professor in the Department of Emergency Medicine, will examine the proteins that are released into the blood during acute stroke. The latter two studies will explore whether blood markers can help predict who will do well and who has greater risks with a given therapy.

Enrollment in the first phase of the NIH-funded Investigational Management of Stroke (IMS) study was already completed this spring. The second phase of the 13-center North American study, headed by Thomas Tomsick, MD, professor of radiology and Dr. Broderick, will test t-PA through the vein and additional t-PA and ultrasound energy delivered by a small tube or catheter at the site of the blocked brain artery.

People with a family history of stroke, brain aneurysm or brain hemorrhage who wish to participate in one of the genetic studies should call Mary Haverbush at (513) 558-3992.



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