In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate

被引：112

作者：

Brichta, Lars

Holker, Irmgard

Haug, Karsten

Klockgether, Thomas

Wirth, Brunhilde

机构：

[1] Univ Cologne, Inst Human Genet, D-50931 Cologne, Germany

[2] Univ Cologne, Inst Genet, D-50931 Cologne, Germany

[3] Univ Cologne, Ctr Mol Med, D-50931 Cologne, Germany

[4] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany

[5] Univ Bonn, Dept Neurol, D-5300 Bonn, Germany

来源：

ANNALS OF NEUROLOGY | 2006年 / 59卷 / 06期

关键词：

D O I：

10.1002/ana.20836

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

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页码：970 / 975

页数：6

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