Potential EEG biomarkers and antiepileptogenic strategies for epilepsy in TSC Current therapeutic approaches for epilepsy primarily represent symptomatic treatments that suppress seizures, but have not been demonstrated to prevent epilepsy or modify disease progression. In recent years, there has been tremendous interest in developing disease-modifying or """"""""antiepileptogenic"""""""" therapies. Tuberous Sclerosis Complex (TSC) is a common genetic cause of epilepsy and a subset of TSC patients may represent a rational, feasible population to target an antiepileptogenic treatment approach. First of all, some patients are diagnosed with TSC at a young age before the onset of epilepsy due to the presence of non-neurological findings: The presence of these findings makes it feasible to identify these patients and initiate a potential antiepileptogenic treatment at an early stage of epileptogenesis. Second, these patients are at high risk for developing epilepsy in the future. Because of these factors initiating a therapy with potential side effects in a presymptomatic stage can likely be justified in TSC patients. Finally, the identification of the mTOR pathway in the pathophysiology of TSC suggests that mTOR inhibitors could have antiepileptogenic properties in TSC but there may be significant risks and side effects. Therefore, before initiating an antiepileptogenic drug trial in TSC patients, it would be beneficial to obtain further evidence to optimize the selection criteria and treatment paradigms to maximize efficacy and minimize side effects of mTOR inhibitors, as well as establish a network of preclinical and clinical sites. n this P20 grant application we propose to conduct pre-clinical and clinical studies that establish optimal parameters for a potential antiepileptogenic drug trial. The preclinical core will aim to determine the optimal rapamycin treatment paradigms that maintain antiepileptogenic efficacy but minimize risks of side effects. The clinical core aims to determine whether EEGs during infancy are a reliable biomarker to identify TSC patients that will develop epilepsy and thus appropriate candidates for an antiepileptogenic drug trial. We will also establish the infrastructure for a TSC Epilepsy Center Without Walls, which will facilitate such clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory Grants (P20)
Project #
5P20NS080199-03
Application #
8732713
Study Section
Special Emphasis Panel (ZNS1)
Program Officer
Fureman, Brandy E
Project Start
2012-09-01
Project End
2015-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Hussain, Shaun A; Mathern, Gary W; Hung, Phoebe et al. (2017) Intraoperative fast ripples independently predict postsurgical epilepsy outcome: Comparison with other electrocorticographic phenomena. Epilepsy Res 135:79-86
Capal, Jamie K; Bernardino-Cuesta, Beatriz; Horn, Paul S et al. (2017) Influence of seizures on early development in tuberous sclerosis complex. Epilepsy Behav 70:245-252
Srivastava, Siddharth; Sahin, Mustafa (2017) Autism spectrum disorder and epileptic encephalopathy: common causes, many questions. J Neurodev Disord 9:23
Davis, Peter E; Filip-Dhima, Rajna; Sideridis, Georgios et al. (2017) Presentation and Diagnosis of Tuberous Sclerosis Complex in Infants. Pediatrics 140:
Martin, Katie R; Zhou, Wanding; Bowman, Megan J et al. (2017) The genomic landscape of tuberous sclerosis complex. Nat Commun 8:15816
Capal, Jamie K; Horn, Paul S; Murray, Donna S et al. (2017) Utility of the Autism Observation Scale for Infants in Early Identification of Autism in Tuberous Sclerosis Complex. Pediatr Neurol 75:80-86
Wong, Michael (2016) Commentary: mTOR inhibition suppresses established epilepsy in a mouse model of cortical dysplasia. Epilepsia 57:1349-50
Wu, Joyce Y; Peters, Jurriaan M; Goyal, Monisha et al. (2016) Clinical Electroencephalographic Biomarker for Impending Epilepsy in Asymptomatic Tuberous Sclerosis Complex Infants. Pediatr Neurol 54:29-34
Dölen, Gül; Sahin, Mustafa (2016) Editorial: Essential Pathways and Circuits of Autism Pathogenesis. Front Neurosci 10:182
Ebrahimi-Fakhari, Darius; Saffari, Afshin; Wahlster, Lara et al. (2016) Congenital disorders of autophagy: an emerging novel class of inborn errors of neuro-metabolism. Brain 139:317-37

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