RT期刊文章SR电子T1探索mTOR抑制治疗线粒体疾病(p4.6 - 060)摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯SP p4.6补充92 - 060签证官是15 A1阿比盖尔圣人A1雷首页切尔·萨拉查A1 Kristin Engelstad A1安吉拉Curcio A1亚历山大Khandji A1詹姆斯·加文A1 Darryl De Vivo年2019 UL //www.ez-admanager.com/content/92/15_supplement/p4.6 - 060. -文摘AB目的:探讨抑制mTOR的好处在两个线粒体疾病患者使用雷帕霉素类似物,Everolimus:病人利综合征由于NDUSF4突变,和患者B线粒体脑病、乳酸酸中毒、和类似中风发作(看见)由于MT-TL1, m。3243 G >突变。背景:儿童出现线粒体疾病会导致严重的发病率和死亡率,是无法治愈的。雷帕霉素显著减弱疾病进展在NDUFS4敲除小鼠模型模拟利综合症。本研究鼓励我们对待两个孩子使用雷帕霉素类似物与线粒体疾病,Everolimus。设计/方法:病人被诊断为13个月岁利综合症(纯合子NDUSF4错义突变)。24个月岁,她重要电动机和语音延迟,无法站立或行走,依赖于气管造口术和胃造口术。病人B岁被诊断出4年米拉斯综合症(MT-TL1 m.3243A >)岁半,他低渗的、反应迟钝、癫痫和依赖胃造口术。病人都开始Everolimus (4.5 mg / m2 / d)使用FDA批准协议治疗结节性硬化症患者和室巨细胞星形细胞瘤。结果:患者表现出非凡的对治疗的反应。20个月的治疗后,她在独立与共济失调步态行走,在句子,不再依赖于气管造口术或胃造口术。粗大运动功能测量- 88 2年岁从48.8%提高至83.75%年龄3.8岁。 Repeat brain MRI showed significant improvement.The condition of Patient B, in contrast, continued to deteriorate until his death at age 6.7 years. Brain MRI studies also worsened reflecting this clinical deterioration.Conclusions: Treatment with mTOR inhibitors may be effective in some mitochondrial disorders, but the therapeutic mechanism(s) currently is unclear. Patient A clearly has improved clinically and radiographically reflecting the improvement in model mice with the same nuclear gene mutation.Disclosure: Dr. Sage has nothing to disclose. Dr. Salazar has received research support fromSMA Foundation, Biogen, Roche, AveXis, Mallinckrodt, Ultragenyx, PTC Therapeutics, Sarepta Therapeutics, and the Jain Foundation. . Dr. Engelstad has nothing to disclose. Dr. Curcio has nothing to disclose. Dr. Khandji has nothing to disclose. Dr. Garvin has nothing to disclose. Dr. De Vivo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advisor/consultant for AveXis, Biogen, Cytokinetics, Ionis Pharmaceuticals, Inc., Metafora, Roche, Sanofi, Sarepta, and the SMA Foundation. Dr. De Vivo has received research support from Grants from the Department of Defense, Hope for Children Research Foundation, the National Institutes of Health, and the SMA Foundation; clinical trials funding from Biogen, Mallinckrodt, PTC Therapeutics, Sarepta, and Ultragenyx.