ADC Reviews

Study: Discovery of potential drug targets associated with stroke


In a new study, an international team has identified 89 genetic loci associated with stroke risk and six genes that are potential drug targets for preventing or treating stroke. Of these 89 loci, 61 were newly discovered. The findings are based on data from 2.5 million people of five different ancestry, more than 200,000 of whom had suffered a stroke. Members of the GIGASTROKE consortium conducted the study. The relevant research results were published online in the journal Nature on September 30, 2022, with the title of “Stroke genetics informs drug discovery and risk prediction across ancestries”.

Stroke is the second leading cause of death worldwide, accounting for approximately 12% of all deaths, and a leading cause of loss of life or disability. A locus is the physical location of a gene on a chromosome within a cell.

“The population studied in this paper is fairly globally representative, including Africa, South Asia, East Asia, Europe and Latin America,” said co-author Dr. Sudha Seshadri of the University of Texas Health Science Center at San Antonio. One group that is still not well represented is the Hispanic population in the U.S., so there is still research to be done.”

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

“Stroke and dementia share common biology, and this project uses research methods that study the genetics of stroke,” said co-author Dr. Claudia Satizabal, assistant professor of population health sciences at the University of Texas Health Science Center at San Antonio. This will make us even more powerful in studying dementia.”

Co-author Dr Muralidharan Sargurupremraj said the large-scale project showed the utility of using a variety of approaches, “from genetic loci, genetic variants, to identifying molecules and pathways that could be targets for stroke drugs”.

Seshadri noted that currently known drug targets for Alzheimer’s disease and related dementias have so far not led to effective treatments. “Discovering and studying new biology is one of the most promising avenues for finding new drug targets and drugs to treat dementia,” she said.

In the next 10 years, driven by research such as the GIGASTROKE findings, dementia clinical care will “advance to taking blood samples from patients, looking at their genetics to understand what’s going on in the brain,” she said. targeted treatment”.

Aniket Mishra et al. Stroke genetics informs drug discovery and risk prediction across ancestries. Nature, 2022, doi:10.1038/s41586-022-05165-3.