Valproic Acid and Lamotrigine Differentially Modulate the Telomere Length in Epilepsy Patients

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Abstract
Background/Objectives: Antiseizure drugs (ASDs) are the primary therapy for epilepsy and the choice varies according to the seizure type. Epilepsy patients experience chronic mitochondrial oxidative stress and increased levels of pro-inflammatory mediators, recognizable hallmarks of biological aging, however few studies have explored aging markers in epilepsy. Herein, we addressed for the first time the impact of ASDs on molecular aging by measuring telomere length (TL) and mtDNA copy number (mtDNA-CN). Methods: Using QPCR, in epilepsy patients compared to matched healthy controls (CT), and its association with plasma levels of ASDs and other clinical variables. The sample comprised 64 epilepsy patients and 64 CT. Patients were grouped on monotherapy with lamotrigine (LTG) or valproic acid (VPA), and those treated with a combination therapy (LTG+VPA). Multivariable logistic regression was applied to analyze obtained data. Results: mtDNA-CN was similar between patients and controls, and none of the comparisons were significant for this marker. TL was shorter in not seizure-free patients than CT (1.50±0.35 vs. 1.68±0.34, p<0.05), regardless of the ASD therapy. These patients exhibited the highest proportion of adverse drug reactions. TL was longer in patients on VPA monotherapy, followed by patients on LTG monotherapy and by patients on LTG+VPA combined scheme (1.77±0.24; 1.50±0.32; 1.36±0.37 respectively, p<0.05), suggesting that ASD treatment differentially modulates TL. Conclusions: Our findings suggest that clinicians could consider TL measurements to decide the best ASD treatment option (VPA and/or LTG) to help predict ASD response in epilepsy patients.

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