Irish scientists have identified a potential method of preventing damaging seizures for people with epilepsy. The breakthrough led by researchers in Trinity College Dublin could also have implications for the treatment of other neurological conditions.
Epilepsy is a chronic central nervous system disorder affecting about 1 per cent of the population and 50 million people worldwide. It is characterised by recurrent, spontaneous seizures caused by disrupted electrical activity in the brain.
While the brain accounts for just 2 per cent of human body mass, it expends almost 20 per cent of the body’s daily energy production. To maintain this high energy demand brain cells are nourished by an intricate network of capillaries forming the so-called blood-brain barrier (BBB). Such is the extent of these capillaries, it is estimated every brain cell is essentially nourished by its own capillary.
Fundamentally, it is disruption to the integrity of these capillaries and the BBB that the Trinity scientists believe is a key driver of seizure activity in humans. Critically their research published on Thursday in Nature Communications shows restoring that integrity can prevent seizures.
"Our findings suggest that designing medicines aimed at stabilising the integrity of blood vessels in the brain may hold promise in treating patients who are currently non-responsive to anti-seizure medications," explained Dr Matthew Campbell, associate professor in Trinity's School of Genetics and Microbiology.
“This work represents one of the first conclusive studies that pinpoints a key feature of seizures that has to date not been studied in great molecular detail,” he added.
Seizure activity
Importantly, the work embraces both basic and clinical research involving patients with epilepsy. Using similar techniques in humans and in pre-clinical models, the scientists were able to show that BBB disruption was a key driver of seizure activity.
Added to this, they were able to show restoring BBB integrity could prevent seizures – this finding holds real potential in moving the discoveries closer to a real and meaningful therapy, Dr Campbell said.
Lead author Dr Chris Greene added: "We are excited about the potential our findings hold for advancing the field of epilepsy research as well as other neurological conditions. In fact, stabilising the integrity of blood vessels in the brain could have relevance for a wide range of other diseases and we are just at the beginning of the process in driving the research forward."
On the clinical significance of the findings, Prof Colin Doherty, TCD professor of epilepsy, said it was the culmination of many years of collaboration between clinical and basic research groups, but "it simply wouldn't have been possible without the commitment of patients and their interest in getting involved in research studies aimed at better understanding their condition", he added.
A team of geneticists, neurologists, neuropathologists and neurosurgeons from Trinity; Royal College of Surgeons in Ireland, St James's Hospital, Beaumont Hospital and Uppsala University in Sweden were involved in the study. Additionally, it was part of a collaboration between Trinity and the FutureNeuro research centre funded by Science Foundation Ireland.
The research was also supported by the Irish Research Council; the St James's Hospital foundation and the Ellen Mayston Bates bequest in the Trinity Foundation.
