TY -的T1 -探索mTOR抑制治疗线粒体疾病(p4.6 - 060)摩根富林明-神经学乔-神经学六世- 92 - 15补充SP - p4.6 - 060 AU -阿比盖尔圣人非盟-雷切尔·首页萨拉查盟-克里斯汀Engelstad盟安吉拉Curcio AU -亚历山大Khandji盟-詹姆斯·加文盟Darryl De Vivo Y1 - 2019/04/09 UR - //www.ez-admanager.com/content/92/15_supplement/p4.6 - 060. -文摘N2 -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 A>G mutation.Background: Childhood onset mitochondrial disease causes severe morbidity and mortality and is untreatable. Rapamycin dramatically attenuated disease progression in NDUFS4 knockout model mice simulating Leigh Syndrome. This study encouraged us to treat two children with mitochondrial disease using a rapamycin analogue, Everolimus.Design/Methods: Patient A was diagnosed at age 13 months with Leigh syndrome (homozygous NDUSF4 missense mutation). At age 24 months, she had significant motor and speech delay, was unable to stand or walk, and dependent on tracheostomy and gastrostomy.Patient B was diagnosed at age 4 years with MELAS syndrome (MT-TL1, m.3243A>G.) At age 5-1/2, he was hypotonic, lethargic, epileptic and dependent on gastrostomy.Both patients were started on Everolimus (4.5 mg/m2/d) using the FDA approved protocol for the treatment of patients with tuberous sclerosis and subependymal giant cell astrocytomas.Results: Patient A showed remarkable response to treatment. After 20 months of treatment, she was walking independently with an ataxic gait, speaking in sentences, and no longer dependent on tracheostomy or gastrostomy. The Gross Motor Function Measure-88 had improved from 48.8% at age 2 years to 83.75% at age 3.8 years. 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. ER -