1. Intracerebral delivery of antiseizure medications by microinvasive neural implants.
- Author
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Jackson HD, Cotler MJ, Saunders GW, Cornelssen CA, West PJ, Metcalf CS, Wilcox KS, and Cima MJ
- Abstract
Focal epilepsy is a difficult disease to treat as two-thirds of patients will not respond to oral antiseizure medications (ASMs) or have severe off-target effects that lead to drug discontinuation. Current non-pharmaceutical treatment methods (resection or ablation) are underutilized due to the associated morbidities, invasive nature, and inaccessibility of seizure foci. Less invasive non-ablative modalities may potentially offer an alternative. Targeting the seizure focus in this way may avoid unassociated critical brain structures to preserve function and alleviate seizure burden. Here we report use of an implantable, miniaturized neural drug delivery system [Microinvasive neural implant infusion platform (MINI)] to administer antiseizure medications (ASMs) directly to the seizure focus in a mouse model of temporal lobe epilepsy. We examined the effect local delivery of phenobarbital (PB) and valproate (VPA) had on focal seizures, as well as adverse effects, and compared this to systemic delivery. We show that local delivery of PB and VPA using our chronic implants significantly reduced focal seizures at all doses given. Furthermore, we show that local delivery of these compounds resulted in no adverse effects to motor function, whereas systemic delivery resulted in significant motor impairment. The results of this study demonstrate the potential of ASM micro dosing to the epileptic focus as a treatment option for people with drug resistant epilepsy. This technology could also be applied to a variety of disease states, enabling a deeper understanding of focal drug delivery in the treatment of neurological disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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