Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
Developmental Biology and Cancer University College London Great Ormond Street Institute of Child Health, London, UK.
Epilepsia. 2021 Dec;62(12):3131-3142. doi: 10.1111/epi.17101. Epub 2021 Oct 28.
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy with early childhood onset. Patients with DS do not respond well to antiepileptic drugs and have only a few treatment options available. Here, we evaluated the effect of medium chain triglyceride (MCT) diet therapy in a mouse model of DS.
Scn1a DS mice were given diets supplemented with MCTs with varying ratios of decanoic (C10) and octanoic (C8) acid or a control diet for 4 weeks. Video monitoring was performed to evaluate spontaneous convulsive seizure frequency. Susceptibility to hyperthermia-induced seizures was also examined. Medium chain fatty acids, and mitochondrial and antioxidant markers were assessed in brain homogenate.
Dietary intervention with MCTs significantly prolonged survival and reduced convulsive seizure frequency during the critical period of highest seizure occurrence in the Scn1a DS mice. Moreover, MCT diet therapy showed protective effects against hyperthermia-induced seizures. We demonstrated that coadministration of C10/C8 was effective at reducing both seizures and mortality, whereas C10 alone only reduced mortality, suggesting that the ratio of C10 to C8 in the MCT is an important factor for efficacy. When C10 and C8 are supplemented at an 80:20 ratio in the diet, C10 accumulates in the brain in high enough concentrations to enhance brain energy metabolism by both stimulating mitochondrial enrichment and increasing its antioxidant status.
The results from this study indicate that MCT diet therapy may provide therapeutic benefits in DS. Future clinical studies would elucidate whether these positive effects are mirrored in human patients.
Dravet 综合征（DS）是一种严重的发育性和癫痫性脑病，发病于幼儿期。DS 患者对抗癫痫药物反应不佳，可供选择的治疗方法有限。在此，我们评估了中链甘油三酯（MCT）饮食疗法在 DS 小鼠模型中的疗效。
给予 Scn1a DS 小鼠补充不同比例癸酸（C10）和辛酸（C8）的 MCT 饮食或对照饮食 4 周。进行视频监测以评估自发性惊厥发作频率。还检查了对高热诱导性癫痫发作的易感性。评估脑匀浆中的中链脂肪酸以及线粒体和抗氧化标志物。
MCT 的饮食干预显著延长了 Scn1a DS 小鼠的生存时间，并降低了癫痫发作最频繁的关键期的惊厥发作频率。此外，MCT 饮食疗法对高热诱导性癫痫发作具有保护作用。我们证明，C10/C8 的共同给药可有效降低癫痫发作和死亡率，而 C10 单独给药仅降低死亡率，表明 MCT 中 C10 与 C8 的比例是疗效的重要因素。当饮食中 C10 和 C8 以 80:20 的比例补充时，C10 在大脑中积累到足够高的浓度，通过刺激线粒体富集和增加其抗氧化状态来增强大脑能量代谢。
本研究的结果表明，MCT 饮食疗法可能为 DS 提供治疗益处。未来的临床研究将阐明这些积极影响是否在人类患者中得到体现。
