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Long non-coding RNAs: regulators of epileptogenesis and potential targets for therapy

Epilepsy is chronic neurological disease with no cure. Current therapeutic approaches merely manage symptoms and are ineffective for up to one third of individuals with epilepsy. There is a real unmet clinical need to develop novel therapeutics which treat the underlying pathomechanisms of disease.
We present preliminary data which suggests that a class of non-coding RNAs known as long non-coding RNAs (lncRNA) are perturbed in the brain following epilepsy-inciting events. LncRNAs are critical regulators of many cellular functions and thus this dysregulation may underlie some of the key components of epileptogenesis including large scale disruptions in gene expression and regulation, which in turn give rise to processes such as neuroinflammation, cell loss and aberrant neurogenesis eventually culminating in spontaneous seizure development. The precise function of lncRNAs in epilepsy development however remains unknown.
The current proposal will use a combination of animal models, human resected epilepsy tissue, next generation sequencing and drug screening approaches to generate the first transcriptome-wide analysis of lncRNAs in mouse and human epilepsy and then perform a systematic drug screening approach to identify and target lncRNAs with potential anti-convulsive and anti-epileptogenic properties.
Overall, this proposal will greatly increase our understanding of the molecular mechanisms of epilepsy development as well as shed light on the therapeutic potential of lncRNA targeting to treat the disease.