Addenbrooke's patient Bob Petch is on a trial to see if a drug used to treat epilepsy could help prevent stroke in people whose arteries show signs of atherosclerosis – furring of the arteries.
It's one of the major causes of stroke, particularly among older individuals and people who have high blood pressure, high cholesterol or smoke.
It invovles the hardening and narrowing of the vessels that carry blood from the heart to the brain.
Scientists now think atherosclerosis is due to inflammation.
One of the drugs being trialled in Cambridge is sodium valproate, which has been used for decades to treat individuals with epilepsy.
For patients like Bob Petch, taking part in the research is making a difference.
When I tried to stand up, I realised the right hand side of my body wasn’t doing what I wanted it to.
Bob Petch, CUH patient
Before the pandemic hit, Bob 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.
“I was trying to hang a rail in a wardrobe when I suddenly realised my hands weren’t manoeuvring as they should do."
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.
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.
While at Addenbrooke’s, Bob met CUH 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,” he says.
“I hope they’re successful and are able to find a treatment that can help lots of other people in a similar situation.”
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.
Dr Nick Evans, CUH consultant
Dr Nick Evans from the Department of Clinical Neurosciences at the University of Cambridge said:
“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 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.
Work by Evans’s colleague Professor Hugh Markus showed that people who are on sodium valporate 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.”
Take part in the trial
The team have begun recruiting patients to a small trial at Addenbrooke’s Hospital, part of Cambridge University Hospitals NHS Foundation Trust (CUH).
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 https://www.neurology.cam.ac.uk/neurology-unit-research-groups/stroke-research-group (opens in a new tab).
Cambridge Festival: Future therapies in cardiovascular research
To hear more, Dr Nick Evans will be speaking at the Cambridge Festival this week.
6:30pm-7:30pm on Wednesday 6 April
Cardiovascular diseases are the leading cause of death worldwide, taking millions lives each year. Cardiovascular 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 (opens in a new tab).