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Ann of Neurol:依维莫司可明显降低结节性硬化症患者的癫痫发作

来源:生物谷 2013-07-17 23:04

2013年7月17日 讯 /生物谷BIOON/ --近日,刊登在国际杂志Annals of Neurology上的一篇研究报告中,来自得克萨斯州儿童医院的研究者通过研究表明,一种用于移植器官移植排斥反应的药物,可以明显降低结节性硬化症(tuberous sclerosis complex,TSC)病人的癫痫发作,TSC是一种遗传性疾病,其主要表现为在机体多种器官上产生良性瘤,而且据不完全估计该疾病在全世界影响着超过100万人的健康。

研究者Darcy Krueger表示,依维莫司疗法可以减少TSC病人的发作频率以及发作持续时间(这些患者此前对别的疗法均无反应),有效控制病人的癫痫发作情况和病人较高的生活质量直接相关,而且副作用也比较有限;目前III期临床试验正在揭示这种疗法的效果。

这项研究包括对20名使用依维莫司的个体进行研究,患者的年龄中值为8,其中一半病人加入到辛辛那提儿童医院,而另一半病人进入得克萨斯州儿童医院进行研究。研究者发现,在20个病人中,依维莫司可以降低其中12人50%的疾病发作频率,在20名TSC病人中可以使得其中17人的生存中值降低73%,其中有4人并没有发作,而7人的发作频率降低了至少90%,患者总体的生活质量得到了极大的改善。

在20世纪90年代,研究者追踪了引发TSC疾病的两个基因-TSC1以及TSC2,当这些基因出现缺失时,细胞就会表达高水平的mTOR,这种蛋白可以引发肿瘤细胞以及血管不受控制地生长;而依维莫司可以通过抑制mTORC1来抑制肿瘤生长,而且可以以同样的方式来降低TSC病人的发病。

研究者Krueger表示,依维莫司治疗癫痫症的效应是否可以扩展至TSC病人的治疗还并不清楚,mTORC1参与了遗传性及神经发育相关的综合征,这些主要表现为癫痫症,附加的实验还会揭示是否依维莫司对癫痫症患者而不是与TSC相关的病人有益处。相关研究由诺华制药和Clack基金提供资助。(生物谷Bioon.com)

Everolimus treatment of refractory epilepsy in tuberous sclerosis complex

Darcy A. Krueger MD, PhD1,*, Angus A. Wilfong MD2, Katherine Holland-Bouley MD, PhD1, Anne E. Anderson MD2, Karen Agricola CFNP1, Cindy Tudor CPNP1, Maxwell Mays BS1, Christina M. Lopez BS2, Mi-Ok Kim PhD3, David Neal Franz MD1

Objective: Epilepsy is a major manifestation of Tuberous Sclerosis Complex (TSC). Everolimus is an mTORC1 inhibitor with demonstrated benefit in several aspects of TSC. We report the first prospective human clinical trial to directly assess whether everolimus will also benefit epilepsy in TSC patients. Methods: The effect of everolimus on seizure control was assessed using a prospective, multi-center, open-label, phase I/II clinical trial. Patients ≥2 years of age with confirmed diagnosis of TSC and medically-refractory epilepsy were treated for a total of 12 weeks. The primary end point was percentage of patients with a ≥50% reduction in seizure frequency over a 4-week period before and after treatment. Secondary endpoints assessed impact on electroencephalography (EEG), behavior, and quality of life. Results: 23 patients were enrolled and 20 patients were treated with everolimus. Seizure frequency was reduced by ≥50% in 12 of 20 subjects. Overall, seizures were reduced in 17 of the 20 by a median reduction of 73% (p<0.001). Seizure frequency was also reduced during 23-hour EEG monitoring (p=0.007). Significant reductions in seizure duration and improvement in parent-reported behavior and quality of life were also observed. There were 83 reported adverse events that were thought to be treatment-related, all of which were mild or moderate in severity. Interpretation: Seizure control improved in the majority of TSC patients with medically-refractory epilepsy following treatment with everolimus. Everolimus demonstrated additional benefits on behavior and quality of life. Treatment was safe and well-tolerated. Everolimus may be a therapeutic option for refractory epilepsy in this population. ANN NEUROL 2013. © 2013 American Neurological Association

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