@article{27c9c78ea37c4bfbbe01ec69b0ca8300,
title = "The path from scientific discovery to cures for epilepsy",
abstract = "The epilepsies are a complex group of disorders that can be caused by a myriad of genetic and acquired factors. As such, identifying interventions that will prevent development of epilepsy, as well as cure the disorder once established, will require a multifaceted approach. Here we discuss the progress in scientific discovery propelling us towards this goal, including identification of genetic risk factors and big data approaches that integrate clinical and molecular {\textquoteleft}omics{\textquoteright} datasets to identify common pathophysiological signatures and biomarkers. We discuss the many animal and cellular models of epilepsy, what they have taught us about pathophysiology, and the cutting edge cellular, optogenetic, chemogenetic and anti-seizure drug screening approaches that are being used to find new cures in these models. Finally, we reflect on the work that still needs to be done towards identify at-risk individuals early, targeting and stopping epileptogenesis, and optimizing promising treatment approaches. Ultimately, developing and implementing cures for epilepsy will require a coordinated and immense effort from clinicians and basic scientists, as well as industry, and should always be guided by the needs of individuals affected by epilepsy and their families. This article is part of the special issue entitled {\textquoteleft}New Epilepsy Therapies for the 21st Century – From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy{\textquoteright}.",
keywords = "Animal model, Big data, Biomarker, Cellular model, Cure, Drug-screening, Epigenetics, Epilepsy, Epileptogenesis, Genetics, Optogenetics",
author = "Carvill, {Gemma L.} and Dulla, {Chris G.} and Lowenstein, {Dan H.} and Brooks-Kayal, {Amy R.}",
note = "Funding Information: The area where the most rapid progress towards a cure is being made is in the rare, early-onset severe epilepsies. In part this has been driven by the formation of gene-specific family foundations, including initially the Dravet Sydrome Foundation ( SCN1A ) and the Tuberous Sclerosis Foundation ( TSC1/2 ), but now >30 foundations exist. Many raise funds to sponsor basic research but also increasingly therapies in pre-clinical and even clinical trials. In addition to the family foundations mentioned above, non-profits such as Citizens United for Research in Epilepsy (CURE) and the Epilepsy Foundation will continue to be important support systems for patients, families and scientists alike. The path to finding cures for epilepsy begins with scientific discovery. While the NIH is the biggest sponsor for this research, funds for epilepsy research still lag far behind other common neurological disorders such as Alzheimer's and Parkinson's disease; advocacy will be vital to shift this balance as will continuing to improve the public's awareness of epilepsy in its many forms. With increased competition and lower paylines, there is a need for being strategic in the distribution of funds for epilepsy research, and this was part of the motivation for establishing the NINDS Benchmarks for Epilepsy Research, which have been regularly revised every 5–7 years to stay current with advances in the field ( Long et al., 2016 ). In parallel with these nationwide efforts, non-profit organizations have a crucial role in supporting both young investigators and high-risk projects unlikely to be funded by the NIH. It is our responsibility as scientists to make sure we spend foundation money wisely and ensure the best science gets funded by assisting in grant review and advisory roles. Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",
year = "2020",
month = may,
day = "1",
doi = "10.1016/j.neuropharm.2019.107702",
language = "English (US)",
volume = "167",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
}