Grant round winners 2012

Mesial temporal lobe epilepsy (mTLE) is a common type of focal epilepsy, which affects the hippocampus, parahippocampal gyrus and amygdala of the brain. These structures are located in the temporal lobes and have roles in the complex processes of learning, memory and emotion. People affected by mTLE often suffer significant learning impairment and loss of memory; yet the underlying mechanisms involved are not understood and no effective treatment/preventative measures are currently available.

There is normally a constant generation of new nerves (neurogenesis) in the hippocampus, which is important for learning and memory; however this is significantly reduced in mTLE and might explain, at least in part, the learning and memory problems frequently seen.

Dr Malik Zaben, who will work with colleagues under the supervision of Professor William Gray, at Cardiff University, has recently been awarded £240,589, over 36 months, to carry out a fellowship entitled ‘Developing targeted pharmaceutical strategies for restoring hippocampal learning in temporal lobe epilepsy‘, in which this theory will be explored.

In previous studies, Dr Zaben and colleagues used cultures of human epileptic brain tissue to identify inflammatory pathways that could reduce neurogenesis. They were particularly interested in those that, when blocked, could restore neurogenesis back to normal. The group also showed that increasing neurogenesis using an antidepressant completely reversed learning deficits in animal models of chronic epilepsy, supporting the theory that reduced neurogenesis is a cause of learning impairment.

In the current project, Dr Zaben and colleagues will identify more specifically the molecules that underlie reduced neurogenesis in the hippocampi, and confirm their roles in human tissue using licensed drugs. They then plan to assess the efficacy of these drugs in restoring spatial learning (knowledge of the environment and its orientation) in animal models. If this is successful, Dr Zaben hopes this concept will be taken to clinical (human) trials.

Animal models are very different from humans, and there are a lot of factors that determine whether drugs reach clinical trials. Clinical trials themselves are rigorously regulated and can take several years to complete. If, despite these hurdles, the drugs assessed by Dr Zaben and colleagues are proven to be effective and safe in the restoration of spatial (and other types of) learning, this could potentially have an enormous impact on the quality of life of people with mTLE.