Focal epilepsy is a difficult disease to treat as two-thirds of patients will not respond to oral anti-seizure 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 ASMs directly to the seizure focus in a mouse model of temporal lobe epilepsy. We examined the effect local delivery of phenobarbital and valproate had on focal seizures, as well as adverse effects, and compared this to systemic delivery. We show that local delivery of phenobarbital and valproate 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.

中文翻译：

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通过微创神经植入物进行脑内给药抗癫痫药物


局灶性癫痫是一种难以治疗的疾病，因为三分之二的患者对口服抗癫痫药物 （ASM） 没有反应或具有严重的脱靶效应，导致停药。由于相关的发病率、侵入性和癫痫发作病灶的不可及性，目前的非药物治疗方法（切除或消融）未得到充分利用。侵入性较小的非消融方式可能提供一种替代方案。以这种方式靶向癫痫发作病灶可以避免不相关的关键脑结构，以保持功能并减轻癫痫发作负担。在这里，我们报告了在颞叶癫痫小鼠模型中使用植入式小型化神经药物输送系统 [微创神经植入物输注平台 （MINI）] 将 ASM 直接施用于癫痫发作病灶。我们检查了苯巴比妥和丙戊酸钠的局部递送对局灶性癫痫发作的影响以及不良反应，并将其与全身给药进行了比较。我们表明，使用我们的慢性植入物局部输送苯巴比妥和丙戊酸盐在所有剂量下显着减少了局灶性癫痫发作。此外，我们表明这些化合物的局部递送不会对运动功能产生不利影响，而全身递送会导致显着的运动障碍。这项研究的结果表明，ASM 微量给药对癫痫病灶的潜力作为耐药性癫痫患者的治疗选择。该技术还可以应用于各种疾病状态，从而更深入地了解神经疾病治疗中的局灶性药物递送。