Introduction: Epilepsy is a chronic neurological disorder characterized by recurring, unprovoked seizures. Seizures are caused by abnormal and excesive firing of neurons – the excitable cells in the brain – and when seizures occur they disrupt normal brain function. This can result in loss of consciousness, convulsions, altered sensory experiences and changes to autonomic activity (e.g. breathing, heart rate). In rare cases it can be fatal.
There are 6 million people with active epilepsy in Europe and 300.000 further cases each year. Temporal lobe epilepsy – which affects brain structures including the hippocampus - is the most common syndrome in adults and is also the most prone to pharmacoresistance. People with epilepsy have a 2–3 fold increase in mortality, experience high levels of unemployment and are exposed to stigma and prejudice. Moreover, epilepsy – particularly when poorly controlled by medication – not only damages health, but disrupts many other aspects of living, imposing very significant physical, psychological and social burdens on individuals, families and caregivers.
How can we improve the lives of people with epilepsy? There is no cure for epilepsy and treatment is ineffective in about one third of patients. One way to tackle this problem is to understand more about the epileptogenic process – the changes that occur as networks of brain cells transform to a state capable of generating seizures. Such knowledge may provide new leads for treatment of this condition or perhaps a cure. The overall concept of EpimiRNA is to unravel molecular mechanisms underlying epilepsy and then use this knowledge to target the disease in new ways.
EpimiRNA: The EpimiRNA consortium formed in mid-2012 to investigate the role of a family of recently identified molecules called microRNA. These are short sequences of ribonucleic acid (RNA) – a chemical cousin of DNA – made in all cells. Their job is to control protein levels. They do this by binding to the much larger RNA molecules called messengerRNA that code for proteins. This interferes with the production of proteins.
MicroRNAs are thought to be multi-targeting. That is, a single microRNA can have effects on many different proteins. This is particularly interesting for a disease such as epilepsy because we know that epileptogenesis involves changes to many different processes in the brain. There are changes to the type of receptors and channels on the surface of cells, there is injury, repair, inflammation and re-wiring. We know from past efforts that targeting just one protein often has little effect preventing the development of epilepsy. Research by members of the consortium and other teams has already uncovered microRNAs that control brain cell excitability and have been shown in experiments to affect seizures directly.
Overall objective of EpimiRNA: The overall objective of the EpimiRNA consortium is to explore the role of microRNAs in the development, treatment and diagnosis of temporal lobe epilepsy. Scientists will undertake the first complete analysis of microRNA changes across multiple epilepsy models and human brain tissue to identify the active or missing microRNAs in epilepsy. Experiments will then uncover the targets of these microRNAs and, using the latest computer and mathematical modelling techniques, explain how they influence brain excitability. We will look at the genetic code in patients with temporal lobe epilepsy to see if variation or errors may be changing which microRNAs are present in the brain. We will target microRNAs using gene therapy and other approaches and we will search chemical libraries for new compounds which might affect microRNA levels in cells. Seizures or the injuries that trigger epilepsy may cause the release of tiny amounts of microRNA into the bloodstream which can be detected with very sensitive machines. Clinical trials will therefore look at microRNA levels in blood samples from patients. This may lead to non-invasive tests to help doctors predict who may develop epilepsy or respond best to a particular treatment.
The consortium is supported by a number of small and medium enterprises. These include companies seeking to develop new treatments for epilepsy, new ways to control microRNAs and ways to integrate large amounts of data.