在脊髓性肌萎缩症携带者和接受丙戊酸治疗的患者体内SMN的激活。
In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate.
作者信息
Brichta Lars, Holker Irmgard, Haug Karsten, Klockgether Thomas, Wirth Brunhilde
机构信息
Institute of Human Genetics, University of Cologne, Cologne, Germany.
出版信息
Ann Neurol. 2006 Jun;59(6):970-5. doi: 10.1002/ana.20836.
OBJECTIVE
Spinal muscular atrophy results from loss of the survival motor neuron 1 (SMN1) gene and malfunction of the remaining SMN2. We investigated whether valproic acid can elevate human SMN expression in vivo.
METHODS
Blood was collected from 10 spinal muscular atrophy carriers and 20 spinal muscular atrophy patients treated with valproic acid.
RESULTS
Seven of 10 carriers demonstrated increased SMN messenger RNA and protein levels. SMN2 messenger RNA levels were elevated in 7 patients and unchanged or decreased in 13 patients.
INTERPRETATION
We provide first proof of the in vivo activation of a causative gene by valproic acid in an inherited disease and discuss strategies of monitoring drug response in patients.
目的
脊髓性肌萎缩症是由生存运动神经元1（SMN1）基因缺失以及剩余的SMN2功能异常所致。我们研究了丙戊酸是否能在体内提高人类SMN的表达。
方法
采集了10名脊髓性肌萎缩症携带者以及20名接受丙戊酸治疗的脊髓性肌萎缩症患者的血液。
结果
10名携带者中有7名显示SMN信使核糖核酸和蛋白质水平升高。7名患者的SMN2信使核糖核酸水平升高，13名患者的该水平未变或下降。
解读
我们首次证明了丙戊酸在一种遗传性疾病中可在体内激活致病基因，并讨论了监测患者药物反应的策略。
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