Temporal lobe epilepsy: a step closer to more effective treatments
“I’m still uncontrolled. It completely changes your life. I now can no longer work and have issues getting out because of the unpredictability.” ERUK supporter experience of living with uncontrolled epilepsy.
Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults, and it is often associated with scarring of an important memory structure called the hippocampus. This is known as hippocampal sclerosis. TLE with hippocampal sclerosis (TLE-HS) is notoriously difficult to treat with existing antiepileptic drugs (AEDs), and research into its underlying mechanisms is ongoing, so that more effective treatments can be developed.
“My epilepsy has been uncontrollable for over 35 years and the number of different tablets I’ve taken is immense. It’s very painful at times and as I get older I’m having more injuries.” Another ERUK supporter experience.
Dr Alessandra Princivalle and colleagues, at Sheffield Hallam University, have been exploring a theory that an important protein called GABAB, which is needed for normal inhibition in the brain, is reduced in TLE-HS. This disrupts the crucial balance between excitation and inhibition of neurons and leads to seizures. Their findings are published in the journal, Neuropharmacology.
The researchers used two different types of brain tissue removed from people with TLE-HS during epilepsy surgery: scarred (sclerosed) hippocampal tissue and nearby non-epileptic tissue (from the same person). They also included healthy hippocampal tissue from people with no history of epilepsy, who had donated their brains to research after death (post-mortem). These served as the study controls.
The team used a range of laboratory techniques to quantify the amount of GABAB in each type of sample.
As anticipated, they found a general decrease in GABAB in scarred hippocampal tissue compared to non-epileptic tissue from the same person. However, they saw an increase in GABAB in scarred hippocampal tissue compared with control tissue. This may seem surprising, but it has been observed in previous studies. The researchers do note that it may not be a ‘real’ finding and could be due to natural changes in post-mortem samples. In light of this, they propose that non-epileptic tissue from people with TLE may serve as a better control in these types of studies than post-mortem studies.
These results support earlier findings that GABAB is reduced in people with compared to ‘normal’. Confirmation of disease mechanisms is a vital step towards the development of new therapies, and GABAB could potentially become a target for more effective TLE treatments.
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