Dozens of additional stroke-related genes; potential drug targets identified

Researchers from the University of Texas San Antonio Health Sciences Center (UT Health San Antonio) are part of an international team that has discovered 61 additional genetic loci associated with stroke and six genes that are targets potential for pharmacotherapy to prevent or treat stroke. The results, published today (September 28) in Nature, are in 2.5 million people from five different ancestors, more than 200,000 of whom have had a stroke. Members of the GIGASTROKE consortium conducted the research.

Stroke is the second leading cause of death worldwide, responsible for approximately 12% of total deaths and a major contributor to years of life lost or lived with disability. Loci are the physical locations of genes on chromosomes in cells and have been called genetic street addresses.

Sudha Seshadri, MD

Nature The article’s co-author, Sudha Seshadri, MD, professor of neurology at the Joe R. and Teresa Lozano Long School of Medicine at UT Health San Antonio, is the founding director of the Glenn Biggs Institute of the institution for Alzheimer’s disease and neurodegenerative diseases. She leads the Neurology Task Force of CHARGE, an international consortium that has contributed to new findings.

“The population studied in this article has a fairly global representation, including Africa, South Asia, East Asia, Europe and Latin America,” Seshadri said. “Interestingly, one of the groups that remains underrepresented is the American Hispanic population, so there’s still work to be done.”

Stroke is a major risk factor for dementia, and there is significant overlap between the conditions, Seshadri said. Stroke affects small vessels, endothelial cells that line blood vessels, and cells called pericytes that are important for blood vessel formation and other functions. Vascular cognitive impairment and dementia also affect small vessels, endothelial cells and pericytes, Seshadri said.

Photo of Dr. Claudia Satizabal
Claudia Satizabal, PhD

“There is a common biology between stroke and dementia, and there are research methods used in this project to study the genetics of stroke that will make us stronger in the study of dementia,” said research co-author Claudia Satizabal, PhD, assistant professor of population health sciences at UT Health San Antonio and research fellow at the Glenn Biggs Institute.

Photo by Muralidharan Sargurupremraj, PhD
Muralidharan Sargurupremraj, PhD

Co-author Muralidharan Sargurupremraj, PhD, who worked with collaborators in Bordeaux, France, on the global initiative before joining the Glenn Biggs Institute, said the massive project showed the utility of using multiple methods to “pass loci, genetic variations, to identify molecules and pathways that may be drug targets for stroke.

Currently known drug targets in Alzheimer’s disease and related dementias have not led to effective therapies so far, Seshadri noted. “I really think I’ll find out novel biology and its research is one of the most promising avenues for finding new drug targets and drugs to treat dementia,” she said.

Over the next 10 years, she said, clinical dementia care, fueled by research such as GIGASTROKE’s findings, “will advance to take a blood sample from a patient and see the genetics of the person, and thus understand what is happening in the brain and do targeted treatment.

The Glenn Biggs Institute, in conjunction with the University of Texas Rio Grande Valley, is an Alzheimer’s disease research center designated by the National Institute on Aging, one of the elite centers for the care and dementia research in the United States.

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