Blood Genomics of Anticonvulsant Efficacy in Children

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DESCRIPTION (provided by applicant): The selection of anticonvulsant (AED) therapy for patients with epilepsy is based on the patient's seizure type and AED side effect profile. Since significant individual variation exists in the response to therapy, the ability to identify, either prior to or early in therapy, individuals who will attain long-term seizure freedom with a specific AED would represent a significant advance in epilepsy pharmacotherapy. We propose that the genomic expression of white blood cells prior to or just after drug administration will identify individuals likely to attain seizure freedom. Our preliminary data shows: (1) seizures, stroke, hypoglycemia and hypoxia produce characteristic changes of gene expression in the blood of rats 24 hours later, (2) single seizures produce different changes in gene expression in the blood of adult patients 24 hours later, and (3) valproic acid and carbamazepine monotherapy in children with epilepsy produces changes of gene expression in blood leukocytes that are different for each drug and different from controls. This study will determine if there is a blood genomic pattern associated with AEDs and their efficacy. The aims of this study will be to: (1) Determine if there are unique whole blood genomic expression patterns in children with epilepsy experiencing seizure freedom six months after the initiation of oxcarbazepine or valproic acid; (2) Determine whether there is a pattern of gene expression in whole blood prior to treatment that correlates with seizure freedom at one or six months of therapy; (3) Determine if there is a pattern of gene expression in whole blood at one month of therapy that correlates with seizure freedom at six months of therapy. The hypotheses are: (1) The blood genomic expression patterns in children with epilepsy treated with valproic acid and oxcarbazepine will differ from each other and will differ from the blood samples prior to therapy (2) The blood genomic expression patterns in leukocytes prior to therapy or after one month of therapy will predict which patients will attain seizure freedom from oxcarbazepine or valproic acid therapy. We will study whole blood total RNA using the new human U133 Affymetrix oligonucleotide microarrays that assess over 39,000 transcripts.