Epilepsy Research
Epilepsy, one of the major neurological disorders plaguing mankind, is the collective term for a group of central nervous system (CNS) disorders characterised by repeated occurrences of electroencephalographic and motor events, often including convulsions. It is estimated to affect some 20 to 40 million people worldwide and is more prevalent in children than in adults.
A range of different drugs are currently used in the treatment of epilepsy. However, these drugs are inadequate for many different reasons. Thus, current therapy fails to adequately control approximately 50% of patients with severe complex partial epilepsy; some highly effective drugs produce tolerance whilst others cause foetal malformations; few current drugs are available for paediatric use; side-effects often result in poor patient compliance; and therapy is lacking to prevent epileptogenesis with the result that a significant proportion of patients with head injury or infants with febrile seizures subsequently go on to develop the epileptic syndrome. At present, a physician treating epilepsy is therefore faced with the dilemma of selection of a drug often by 'trial and error', with an effectiveness that may range from 50 to 75% and that is frequently associated with significant unwanted effects. For these reasons there is currently an ongoing search for new and better anti-epileptic drugs. A thorough understanding of the mechanisms of seizure generation and spread in the brain is essential for the successful development of such novel therapeutic strategies.
Our research is broadly concerned with the elucidation of the mechanisms of control of excitatory amino acid neurotransmitter release in the mammalian brain and on defining the role that these excitatory transmitters (principally glutamate and aspartate) and the inhibitory neurotransmitter GABA play in the development, triggering and spread of epileptic neuronal hyperactivity in the brain. In addition, we are investigating the anticonvulsant activity, toxicity and potential therapeutic usefulness of a range of established and more novel agents acting at glutamatergic and aspartatergic synapses in the CNS. These include NMDA- and non-NMDA sub-type glutamate receptor antagonists and metabotropic glutamate receptor agonists and antagonists, acting pre- and/or post-junctionally at the central excitatory synapses.
The results of this research are extending our understanding of excitatory amino acid-mediated neurotransmission in the mammalian CNS and are defining the role of the principal excitatory and inhibitory brain neurotransmitters in the mechanisms of development and expression of seizure activity. This work has direct clinical relevance in relation to the development of urgently needed novel drugs for the treatment of refractory forms of epilepsy, in particular complex partial epilepsy.
