Department of Neurology, Columbia University Irving Medical Center, New York, New York, 10032.
Neuroradiology Division, Radiology Department, Columbia University, New York University Irving Medical Center, Milstein Hospital Room 3-101, 177 Fort Washington Avenue, New York, New York, 10032.
Ann Clin Transl Neurol. 2019 Sep;6(9):1877-1881. doi: 10.1002/acn3.50846. Epub 2019 Aug 6.
Leigh syndrome and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) are two of the most frequent pediatric mitochondrial diseases. Both cause severe morbidity and neither have effective treatment. Inhibiting the mammalian target of rapamycin (mTOR) pathway has been shown in model mice of Leigh syndrome to extend lifespan and attenuate both the clinical and pathological progression of disease. Based on this observation, we treated two children with everolimus, a rapamycin analogue. The child with Leigh syndrome showed sustained benefit, while the child with MELAS failed to respond and died of progressive disease. We discuss possible mechanisms underlying these disparate responses to mTOR inhibition.
Leigh 综合征和 MELAS（线粒体脑肌病、乳酸酸中毒和卒中样发作）是两种最常见的儿科线粒体疾病。这两种疾病都会导致严重的发病率，且都没有有效的治疗方法。在 Leigh 综合征的模型小鼠中，抑制哺乳动物雷帕霉素靶蛋白（mTOR）通路已被证明可以延长寿命，并减轻疾病的临床和病理进展。基于这一观察结果，我们用雷帕霉素类似物依维莫司治疗了两名儿童。 Leigh 综合征患儿持续受益，而 MELAS 患儿无反应并死于疾病进展。我们讨论了对 mTOR 抑制产生不同反应的可能机制。
