Epilepsy drug could help prevent stroke in people with ‘furred’ arteries

A drug used to treat epilepsy patients could help prevent stroke in people whose arteries show signs of atherosclerosis – furring of the arteries – scientists will tell audiences at the Cambridge Festival this week.

One of the major causes of stroke, particularly among older individuals and people who have high blood pressure, high cholesterol or smoke, is atherosclerosis, hardening and narrowing of the vessels that carry blood from the heart to the brain. It is caused by the build-up of abnormal material called plaques – collections of fat, cholesterol, calcium and other substances circulating in the blood.

While once over it was thought that it was the narrowing of the arteries that led to stroke, scientists now think it is due to inflammation. The body’s immune system causes damage to the plaques, causing blood clots to form on the surface of the wall, which can break away and travel to the heart or brain, where they can lead to potentially serious problems.

“Treatments for carotid atherosclerosis haven’t really progressed in the last 30 years or so: it’s generally surgery or aspirin. But for frailer individuals, surgery may not be an option, so we really need to find better drugs to help manage their condition.”

_{Dr Nick Evans, Department of Clinical Neurosciences, University of Cambridge}

Dr Evans and colleagues are particularly interested in repurposing existing drugs. These drugs will have already been through safety trials, removing one of the major hurdles facing any new medication.

One of the drugs that they are interested in is sodium valproate, a drug that has been used for decades to treat individuals with epilepsy. Work by Evans’s colleague Professor Hugh Markus showed that people who are on this medication are less likely to experience stroke than the general population, and also less likely than epilepsy patients taking other antiepileptic drugs.

When the team studied the plaques that build up in atherosclerosis, they found higher than anticipated levels of an enzyme known as HDAC9, which helps control the activity of other genes. Sodium valproate appears to inhibit the activity of HDAC9.

“Drugs that inhibit the activity of a number of HDAC enzymes are already being used to treat cancers such as gastrointestinal cancers and leukaemia,” says Dr Evans, “but because they are – with good reason – targeting a number of these enzymes at the same time, they have strong side effects, so wouldn’t be suitable to atherosclerosis. But a drug that targets just the key enzyme would work with far fewer side effects – and that’s what we think we’ve found with sodium valproate.”

The team have begun recruiting patients to a small trial at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust. Patients on the trial will be randomised, with some receiving sodium valproate in addition to their normal medication over a two year period. They will undergo MRI scans to look at the degree of narrowing of their arteries and PET scans to measure inflammation. If the drug appears to be beneficial, the team will move to a phase 3 clinical trial – a much larger scale trial.

Recruitment is underway for patients in the East of England who have had a stroke within the previous six months.

To find out more about the trial, visit the Stroke Research Group website.

When Bob Petch retired from his job as an aircraft electrician at the age of 73, he was determined to keep himself active. Now at the age of 81, he enjoys nothing better than touring the UK with his wife in their motor home. In his local village of Gamlingay, Cambridgeshire, he sits on the Parish Council and acts as a trustee of the local community centre. And before the pandemic hit, he was attending his local gym three times a week, and even now every day he does exercises and takes his dog on an hour brisk walk.

Despite this, however, Bob’s health took a knock last October.

“It was really strange,” he says. “I was trying to hang a rail in a wardrobe when I suddenly realised my hands weren’t manoeuvring as they should do. I found myself leaning against the wardrobe door and when I tried to stand up, I realised the right hand side of my body wasn’t doing what I wanted it to.”

After 10-15 minutes, Bob managed to get control of his movement back and made his way to the bed, where his wife found him. “She asked me if I was OK, but I couldn’t get my mouth to make the shapes for the words to reply.”

By the time the ambulance arrived, his speech had returned, though he had another minor episode on the way to Addenbrooke’s Hospital. He was kept in for two nights for observation. Doctors told him he had had a transient ischaemic attack (TIA) – often referred to as a ‘mini stroke’ – as a result of atherosclerosis.

Fortunately, Bob made a quick and full recovery and is back to his active retirement. The only drawback, he says, is that he now needs to take blood thinners to reduce the risk of another stroke – “which means I feel the cold!”

While at Addenbrooke’s, Bob met consultant and University of Cambridge professor Hugh Markus, who invited him to take part in a new trial to see if sodium valproate could help protect him against future strokes. Bob jumped at the chance and is now trialling the epilepsy drug, returning to the hospital regularly for check-ups and scans to see whether the drug is working.

“What the team are doing is really great. I hope they’re successful and are able to find a treatment that can help lots of other people in a similar situation.”

_{Bob Petch}

Cardiovascular diseases are the leading cause of death worldwide, taking millions lives each year. These diseases include Stroke, Heart Failure, Aorta Disease and Vascular Disease.

The last few decades have seen many successful preventative measures and treatments being developed. These range from highly effective drug therapies to non-pharmacological treatment. Join our team of researchers to discuss their work in the cardiovascular area, and the future therapies being developed to treat these disorders.

Speakers:

• Prof Christi Deaton, Professor of Nursing
• Dr Nick Evans, Consultant in Stroke Medicine
• Dr Tian Zhao, Clinical Lecturer in Cardiovascular Medicine
• Dr Meritxell Nus, BHF Intermediate Research Fellow

For further information and to reserve a place, visit the Cambridge Festival website.

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