An integrated systems-level framework for deciphering multidrug resistant epilepsy.

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Epilepsy is a serious, common neurological disease - one in 26 people will develop epilepsy at some point in their life. Epilepsy has huge public health significance - it is the 5th most disabling disease in the World Health Organisation's rankings of disability by illness and accounts for 3% of all A&E attendances in the UK NHS alone. The greatest burden falls on the 20-30% of people with epilepsy who continue to have uncontrolled seizures despite all currently available antiepileptic drugs. These people are at a significantly increased risk of dying, as well as from other complications of their epilepsy such as memory and cognitive difficulties, and under and unemployment. Surprisingly, there has been no progress in improving seizure control in the last 50 years of anti-epileptic drug development, and none of the current antiepileptic drugs are disease modifying or curative. This absence of progress despite decades of research mandates a new scientific approach. Our project brings together three leading universities in the UK (Imperial College, University College London, Cambridge University) to combine data and expertise in order to address this major unmet clinical need. Our goal is ambitious - to find better drugs for treating epilepsy. Our project combines the largest and most comprehensive genetic datasets on drug response in epilepsy worldwide with proven "big-data" computational methods for working out how genes interact with each other to cause disease. Then, using the latest methods to connect disease mechanisms to drug targets, we aim to translate these insights to new therapies for people living with drug resistant epilepsy. Our project has the potential to transform the lives of people with drug resistant epilepsy, and to inform fundamental mechanisms of human brain function in health and disease generally.