What is the problem?
Epilepsy affects about 1% of the population; approximately 6 million people in the EU have epilepsy with an incidence of about 300,000 new cases per year. In Europe alone, approximately 2 million (0.3% of the population), continue to have seizures despite optimal medical treatment.
Unfortunately, new drugs for epilepsy have had little impact on this group, and so new targets and approaches for drug development are needed. Moreover, many people develop epilepsy following a brain insult such as a head injury, stroke or prolonged seizure (status epilepticus), yet none of our present treatments either prevent the development of epilepsy or modify the prognosis of epilepsy.
As our understanding of the brain has advanced, it has become increasingly apparent that the proteins that surround nerve cells - the extracellular matrix (ECM) - are not only important for maintaining the structural integrity of the brain as a sort of “scaffold” but play key roles in regulating the excitability of the brain and the way that nerve cells behave.
Some genetic epilepsies are caused by mutations in genes that encode ECM-related proteins, yet the effects and impact of these mutations are not fully understood. Also, the way that the ECM changes during the development of epilepsy following a brain insult and the role that these changes play in epilepsy remain unknown. Moreover, drugs and other therapeutic approaches that target the ECM could provide a completely new way to treat epilepsy and to prevent or modify the condition.
Why is it important for society?
Epilepsy is one of the commonest serious neurological conditions. Patients with drug resistant epilepsy have a yearly mortality of 0.5-1% due to sudden unexpected death in epilepsy (SUDEP) which mostly affects young adults. In addition, drug resistant epilepsy is associated with high rates of depression, suicide, accidents, and social exclusion. In 2010, the estimated cost of epilepsy per year in the EU was €14 billion, most of which was attributed to indirect costs such as under-and unemployment, and most of which is due to drug resistant epilepsy. Providing novel therapies to treat and prevent epilepsy could, therefore, have a substantial societal impact. Beyond this, a greater understanding of how the ECM regulates brain excitability and therapies that target ECM-related proteins may have relevance to many other neurological conditions such as dementia, stroke and head injury.
What are the overall objectives?
The overarching objective of this project is to understand the part that change in the ECM play in the development and maintenance of epilepsy and to determine ways to target the ECM to treat epilepsy. Within this, we had specific objectives (i) to understand how the ECM changes during the development of epilepsy (epileptogenesis), (ii) to identify ECM-related components that can serve as biomarkers to predict those who will develop epilepsy, (iii) to identify targets for prevention of epilepsy-related ECM alterations, (iv) to identify targets that can help treat established epilepsy, and (v) to undertake preclinical testing of these biomarkers and treatments in order to facilitate eventual translation to the clinic.
A further important objective was the scientific training and education of early-stage researchers (ESRs) across Europe in order to enrich the European scientific community.
