Breakthrough study finds clues for ‘silent’ stroke treatment

Breakthrough study finds clues for ‘silent’ stroke treatment

A team of scientists have uncovered the genes that are responsible for lacunar, or ‘silent’, strokes, pointing to clues for new treatments.

Silent strokes are a major cause of vascular dementia and difficult to treat. The findings from a decade-long study funded by the British Heart Foundation have discovered changes to 12 genetic regions in the DNA of people who have had a lacunar stroke – a type of stroke caused by weakening of the small blood vessels deep within the brain.

Dr Matthew Traylor, first author of the study at Queen Mary University of London, said: “Genetics offers one of the few ways we can discover completely new insights into what causes a disease such as lacunar stroke. It is only by better understanding of what causes the disease that we will be able to develop better treatments.”

The study has been published in The Lancet Neurology.

Lacunar strokes

Over time, damage to the blood vessels from these strokes, and subsequent interruption to blood flow, can lead to long-term disability, causing difficulty with thinking, memory, walking and ultimately dementia, and it is not usually until someone has had a number of lacunar strokes that there are signs of dementia. Unfortunately, there are currently limited proven treatments.

Professor Hugh Markus and his team at the University of Cambridge have been working with researchers from around the world for the past ten years, and now believe their genetic breakthrough holds the key to finding much-needed treatments for lacunar stroke and vascular dementia.

By scanning and comparing the genetic code of 7,338 patients who had a lacunar stroke with 254,798 people who had not, the researchers discovered that many of the 12 genetic regions linked to lacunar strokes were involved in maintaining the neurovascular unit – the part of the brain that separates the blood vessels from the brain and ensures that nerves function normally. These genetic changes are thought to make the small blood vessels ‘leakier’, causing toxic substances to enter the brain.

Professor Hugh Markus, BHF-funded researcher, leader of the study and neurologist at the University of Cambridge, said: “These small and often silent lacunar strokes have gone under the radar for a long time, and so we haven’t been able treat patients as well as we’d like to. Although small, their consequences for patients can be enormous. They cause a quarter of all strokes and they are the type of stroke which is most likely to lead to vascular dementia.

“We now plan to use this new genetic blueprint as a springboard to develop much-needed treatments to prevent lacunar strokes from occurring in the first place and to help stave off dementia.”

The study also found that high blood pressure, Type 2 diabetes, and a history of smoking are causally associated with an increased risk of lacunar stroke.

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation and cardiologist, said: “This is the most extensive genetic search to date which truly gets to grips with what cause lacunar strokes. These findings are a significant leap forward and we now have a much greater understanding of the genetics and biology behind what causes the small blood vessels deep in the brain to become diseased.

“Lacunar strokes affect around 35,000 people in the UK each year. This research provides real hope that we can prevent and treat this devastating type of stroke much better in the future.”

The team now plan to test whether new treatments can correct these abnormalities on brain cells in the lab and hope to begin human clinical trials in the next ten years.

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