The Lancet：依维莫司可明显抑制结节性硬化症的发展

2012年11月20日 --近日，刊登在国际杂志The Lancet上的一篇研究报告中，来自辛辛那提儿童医院的研究者表示，一种用于治疗移植器官排斥反应的药物可以明显降低结节性硬化症（TSC）患者的脑瘤发展，结节性硬化症是一种在机体重要器官上引发肿瘤的遗传性疾病。

研究揭示了药物依维莫司在抑制结节性硬化症病人脑瘤生长上所表现出的作用。III期临床试验中，研究者对117名患有TSC病症的患者随机使用药物依维莫司和安慰剂进行治疗，随后研究者用MRI技术对患者的肿瘤体积进行监测。

基于此前的研究，美国FDA已经批准了依维莫司用于对病人的治疗，而这项最新研究又再次肯定了前期研究的结果，研究者表示，脑积水通常和脑瘤发生相关，因为它们位于大脑最深处。研究者发现，在TSC患者过度生长的肿瘤细胞中发现的mTOR途径也在癌症和其它病症中被发现，比如阿尔兹海默氏症，II型糖尿病以及帕金森疾病等，这就使得依维莫司-mTOR的抑制剂成为了治疗mTOR相关疾病最好的候选药物。

在美国，大约有50，000个儿童和成年人患有TSC疾病，全世界几乎有100万人患有此病，研究者的这项研究对于开发治疗结节性硬化症的疗法提供了新的希望。

与硬化症相关的拓展阅读：

• JCI：血脑屏障的免疫交换或助力多发性硬化症研究
• FDA批准Tecfidera治疗多发性硬化症
• PLOS ONE:抗癌药伊马替尼可缓解多发性硬化症
• NEJM：新药物BG-12有助防止多发性硬化症复发
• Cell Rep：治疗肌萎缩性脊髓侧索硬化症的新靶点MuSK 更多信息请点击：有关硬化症更多资讯

Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial

Background Tuberous sclerosis complex is a genetic disorder leading to constitutive activation of mammalian target of rapamycin (mTOR) and growth of benign tumours in several organs. In the brain, growth of subependymal giant cell astrocytomas can cause life-threatening symptoms—eg, hydrocephalus, requiring surgery. In an open-label, phase 1/2 study, the mTOR inhibitor everolimus substantially and significantly reduced the volume of subependymal giant cell astrocytomas. We assessed the efficacy and safety of everolimus in patients with subependymal giant cell astrocytomas associated with tuberous sclerosis complex. Methods In this double-blind, placebo-controlled, phase 3 trial, patients (aged 0—65 years) in 24 centres in Australia, Belgium, Canada, Germany, the UK, Italy, the Netherlands, Poland, Russian Federation, and the USA were randomly assigned, with an interactive internet-response system, in a 2:1 ratio to oral everolimus 4·5 mg/m2 per day (titrated to achieve blood trough concentrations of 5—15 ng/mL) or placebo. Eligible patients had a definite diagnosis of tuberous sclerosis complex and at least one lesion with a diameter of 1 cm or greater, and either serial growth of a subependymal giant cell astrocytoma, a new lesion of 1 cm or greater, or new or worsening hydrocephalus. The primary endpoint was the proportion of patients with confirmed response—ie, reduction in target volume of 50% or greater relative to baseline in subependymal giant cell astrocytomas. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00789828. Findings 117 patients were randomly assigned to everolimus (n=78) or placebo (n=39). 27 (35%) patients in the everolimus group had at least 50% reduction in the volume of subependymal giant cell astrocytomas versus none in the placebo group (difference 35%, 95% CI 15—52; one-sided exact Cochran-Mantel-Haenszel test, p<0·0001). Adverse events were mostly grade 1 or 2; no patients discontinued treatment because of adverse events. The most common adverse events were mouth ulceration (25 [32%] in the everolimus group vs two [5%] in the placebo group), stomatitis (24 [31%] vs eight [21%]), convulsion (18 [23%] vs ten [26%]), and pyrexia (17 [22%] vs six [15%]). Interpretation These results support the use of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis. Additionally, everolimus might represent a disease-modifying treatment for other aspects of tuberous sclerosis. Funding Novartis Pharmaceuticals.