Improving memory in mesial temporal lobe epilepsy

Grant round winners 2013

Mesial temporal lobe epilepsy (mTLE) is the most common form of epilepsy in adults, and seizures normally originate in the hippocampi (singular=hippocampus – important memory centres within the temporal lobes) and other related structures. Imaging of affected individuals frequently shows scarring of the hippocampus, and this is known as hippocampal sclerosis. Unsurprisingly, learning and memory dysfunction are very commonly seen in people with mTLE; however because the mechanisms behind these deficits are poorly understood, there are currently no effective treatments for them.

New neurons are continually formed in the hippocampus throughout adulthood, in a process known as neurogenesis, and this is crucial to memory function. In mTLE, neurogenesis is permanently reduced, and this may explain, at least in part, the learning and memory problems that result. In a previous Epilepsy Research UK grant, Professor Liam Gray and colleagues, at the University of Southampton, showed that treatment with the antidepressant fluoxetine (the active ingredient of Prozac) restored neurogenesis in a rodent model of TLE; and that a complex type of spatial/navigational learning (known as allocentric learning) returned to normal.

Professor Gray, now at Cardiff University, and colleagues, have been awarded £148,522, over 24 months, to carry out a project entitled Does Fluoxetine restore spatial learning and memory deficits in patients with mesial temporal lobe epilepsy?; in which they will explore the effectiveness of fluoxetine in restoring allocentric learning, and a specific type of memory, in humans with drug-resistant mTLE.

During the study, participants will be asked to complete a series of standardised learning and memory assessments. They will then be randomly assigned to either a fluoxetine group (to be given oral fluoxetine therapy) or a placebo group (to be given an inactive but identical looking tablet). Following a two-month course of the appropriate therapy, the learning and memory assessments will be repeated and the results will be analysed to see whether or not the subjects treated with fluoxetine show a significant improvement.  Magnetic resonance imaging (MRI) will also be used to try and identify any structural abnormalities that underlie learning and memory problems in mTLE, and find out which patients (if any) benefit most from fluoxetine treatment.

If fluoxetine is shown to significantly improve memory and learning in mTLE, it could have enormous implications in terms of improving people’s quality of life.  Moreover, as a drug that is already licensed, fluoxetine could potentially be approved as part of mTLE treatment in as little as 12 months.

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