In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate
L Brichta, I Holker, K Haug… - Annals of Neurology …, 2006 - Wiley Online Library
L Brichta, I Holker, K Haug, T Klockgether, B Wirth
Annals of Neurology: Official Journal of the American Neurological …, 2006•Wiley Online LibraryObjective 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 …
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 …
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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