Neuromodulation Program, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Ann Clin Transl Neurol. 2023 Sep;10(9):1695-1699. doi: 10.1002/acn3.51851. Epub 2023 Jul 14.
Dravet syndrome (DS) is a monogenic, often refractory, epilepsy resultant from SCN1A haploinsufficiency in humans. A novel therapeutic target in DS that can be engaged in isolation or as adjunctive therapy is highly desirable. Here, we demonstrate reduced expression of the rodent glutamate transporter type 1 (GLT-1) in a DS mouse model, and in wild type mouse strains where Scn1a haploinsufficiency is most likely to cause epilepsy, indicating that GLT-1 depression may play a role in DS seizures. As GLT-1 can be upregulated by common and safe FDA-approved medications, this strategy may be an attractive, viable, and novel avenue for DS treatment.
德拉维特综合征(DS)是一种单基因疾病,常表现为耐药性癫痫,其病因是人类 SCN1A 单倍不足。DS 中一个新的治疗靶点是谷氨酸转运体 1(GLT-1),它可以单独使用或作为辅助治疗。在这里,我们在 DS 小鼠模型中发现 GLT-1 的表达降低,在野生型小鼠品系中也发现 GLT-1 的表达降低,而 Scn1a 单倍不足最有可能导致癫痫,这表明 GLT-1 抑制可能在 DS 发作中起作用。由于常见且安全的美国食品和药物管理局 (FDA) 批准的药物可以上调 GLT-1,因此这种策略可能是一种有吸引力、可行和新颖的 DS 治疗途径。