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3. Issues related to development of new antiseizure treatments

Author

Wilcox, Karen S, Dixon‐Salazar, Tracy, Sills, Graeme J, Ben‐Menachem, Elinor, White, H Steve, Porter, Roger J, Dichter, Marc A, Moshé, Solomon L, Noebels, Jeffrey L, Privitera, Michael D, and Rogawski, Michael A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Neurodegenerative, Epilepsy, Brain Disorders, Neurological, Adult, Animals, Anticonvulsants, Child, Disease Models, Animal, Drug Discovery, Drug Evaluation, Drug Industry, Drugs, Investigational, Humans, Research Support as Topic, Translational Research, Biomedical, Antiseizure drug, Pharmacoresistant epilepsy, Animal models of epilepsy, Translational Medical Research, Neurology & Neurosurgery, Clinical sciences
Abstract

This report represents a summary of the discussions led by the antiseizure treatment working group of the International League Against Epilepsy (ILAE)/American Epilepsy Society (AES) Working Groups joint meeting in London (London Meeting). We review here what is currently known about the pharmacologic characteristics of current models of refractory seizures, both for adult and pediatric epilepsy. In addition, we address how the National Institute of Neurological Disorders and Stroke (NINDS)-funded Anticonvulsant Screening Program (ASP) is evolving to incorporate appropriate animal models in the search for molecules that might be sufficiently novel to warrant further pharmacologic development. We also briefly address what we believe is necessary, going forward, to achieve the goal of stopping seizures in all patients, with a call to arms for funding agencies, the pharmaceutical industry, and basic researchers.

Published
2013

20. Genetic Variation in PADI6-PADI4 on 1p36.13 Is Associated with Common Forms of Human Generalized Epilepsy

Author

Buono, Russell J., primary, Bradfield, Jonathan P., additional, Wei, Zhi, additional, Sperling, Michael R., additional, Dlugos, Dennis J., additional, Privitera, Michael D., additional, French, Jacqueline A., additional, Lo, Warren, additional, Cossette, Patrick, additional, Schachter, Steven C., additional, Basehore, Heather, additional, Lohoff, Falk W., additional, Grant, Struan F. A., additional, Ferraro, Thomas N., additional, and Hakonarson, Hakon, additional

Published
2021
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27. Genetic variation in PADI6-PADI4 on 1p36.13 is associated with common forms of human generalized epilepsy

Author

Buono, Russell J., Bradfield, Jonathan P., Wei, Zhi, Sperling, Michael R., Dlugos, Dennis J., Privitera, Michael D., French, Jacqueline A., Lo, Warren, Cossette, Patrick, Schachter, Steven C., Basehore, Heather, Lohoff, Falk W., Grant, Struan F.A., Ferraro, Thomas N., Hakonarson, Hakon, Buono, Russell J., Bradfield, Jonathan P., Wei, Zhi, Sperling, Michael R., Dlugos, Dennis J., Privitera, Michael D., French, Jacqueline A., Lo, Warren, Cossette, Patrick, Schachter, Steven C., Basehore, Heather, Lohoff, Falk W., Grant, Struan F.A., Ferraro, Thomas N., and Hakonarson, Hakon

Abstract

We performed a genome-wide association study (GWAS) to identify genetic variation associated with common forms of idiopathic generalized epilepsy (GE) and focal epilepsy (FE). Using a cohort of 2220 patients and 14,448 controls, we searched for single nucleotide polymorphisms (SNPs) associated with GE, FE and both forms combined. We did not find any SNPs that reached genome-wide statistical significance (p ≤ 5 × 10−8) when comparing all cases to all controls, and few SNPs of interest comparing FE cases to controls. However, we document multiple linked SNPs in the PADI6-PADI4 genes that reach genome-wide significance and are associated with disease when comparing GE cases alone to controls. PADI genes encode enzymes that deiminate arginine to citrulline in molecular pathways related to epigenetic regulation of histones and autoantibody formation. Although epilepsy genetics and treatment are focused strongly on ion channel and neurotransmitter mechanisms, these results suggest that epigenetic control of gene expression and the formation of autoantibodies may also play roles in epileptogenesis.

Published
2021

46. Introduction

Author

Privitera, Michael D. and Brenner, Richard P.

Published
2002

47. Introduction

Author

Privitera, Michael D.

Published
2001

50. Reply to

Author

Alsherbini, Khalid A., primary, Metter, E. Jeffrey, additional, Foreman, Brandon P., additional, and Privitera, Michael D., additional

Published
2019
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